A search conducted at Indiana University, Bloomington, Indiana
TI: Heat shock and cytokines modulate the expression of adhesion molecules on different human gastric-cancer cell lines.
AU: Hsieh-MC; Wu-CW; Wu-LH; Lui-WY; P'eng-FK; Yu-CL
AD: Department of Surgery, Veterans General Hospital-Taipei, National Yang-Ming University School of Medicine, Republic of China.
SO: Int-J-Cancer. 1996 Sep 4; 67(5): 690-4
ISSN: 0020-7136
PY: 1996
LA: ENGLISH
CP: UNITED-STATES
AB: In order to understand the expression and modulation of adhesion molecules (AMs) on the surface of different gastric cancers, we studied 4 gastric-cancer cell lines including SC-M1, KATO-III, AGS and AZ-521. The expression of E-cadherin, integrins (beta1, beta2 and beta3), ICAMs (1 and 2), and CD11 (a, b and c) on the cells was detected by flow cytometry. We found that E-cadherin was only expressed on SC-M1 and KATO-III. CD29 (beta1 integrin) could be found in cells of all 4 lines. CD54 (ICAM- 1) could not be detected in AZ-521. In contrast, CD18 (beta2 integrin), CD61 (beta3 integrin), ICAM-2, CD11a, CD11b and CD11c were all absent from these cells. Heat-shock treatment (42.5 degrees C, 60 min) enhanced the expression of E-cadherin, CD29 and CD54 on SC-M1, and of CD29 on AGS. In addition, TNF-alpha (50U/ml) and IL-1beta (10U/ml) modulated the expression of these AMs, like heat-shock treatment. The increment of these adhesion molecules caused by heat shock, TNF-alpha and IL-1beta stimulation on SC-M1 was also confirmed by Western blot analysis. Functionally, these treatments increased the binding between normal human mononuclear cells and SC-Ml cells. The heat-shock treatment could induce a significant amount of TNF-alpha and IL-1beta release from SC-M1 and KATO-III, but seemed irrelevant to the expression of AMs. These results suggest that limited adhesion molecules were expressed on the surface of different gastric cancer cells. Heat shock, IL-1beta and TNF-alpha may selectively modulate the expression of these 3 molecules on some of the cells, and this is probably related to their antitumor effect.
MESH: Antigens,-CD-metabolism; Antigens,-CD11-metabolism; Blotting,-Western; Cadherins-metabolism; Flow-Cytometry; Integrins-metabolism; Intercellular-Adhesion-Molecule-1-metabolism; Interleukin-1-pharmacology; Tumor-Cells,-Cultured; Tumor-Necrosis-Factor-pharmacology
MESH: *Cell-Adhesion-Molecules-metabolism; *Cytokines-pharmacology; *Heat-; *Stomach-Neoplasms-metabolism
TG: Human
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0; 0; 0; 126547-89-5
NM: intercellular-adhesion-molecule-2; Antigens,-CD; Antigens,-CD11; Cadherins; Cell-Adhesion-Molecules; Cytokines; Integrins; Interleukin-1; Tumor-Necrosis-Factor; Intercellular-Adhesion-Molecule-1
AN: 96376788
UD: 9612
MEDLINE EXPRESS (R) 1/96-12/96 2 of 125
TI: Fibronectin modulates interleukin 6 and fibronectin synthesis of human glomerular mesangial cells in culture.
AU: Schieren-G; Burger-A; Braunger-M; Filsinger-S; Hansch-GM
AD: Institut fur Immunologie der Universitat Heidelberg, Deutschland.
SO: Exp-Nephrol. 1996 Jan-Feb; 4(1): 48-55
ISSN: 1018-7782
PY: 1996
LA: ENGLISH
CP: SWITZERLAND
AB: In this paper we report that fibronectin (FN) and its proteolytic 120-kD fragment regulate synthesis and secretion of interleukin 6 (IL-6) and of FN by human glomerular mesangial cells. While intact FN and a fragment derived from the heparin-binding domain had no effect on IL-6 secretion, the 120-kD FN fragment containing the cell attachment site stimulated secretion by 40-fold. The same FN fragment reduced FN secretion and the steady state mRNA level by 80%. The intact FN showed only a weak inhibitory effect (+/- 30%); the 30-kD fragment containing the heparin-binding domain had no effect. The effects of the 120-kD FN were inhibited by the peptide RGDS, implying participation of the cell attachment site in signal transduction. An antibody to the alpha-chain of VLA-3 mimicked the effect of the 120-kD FN, whereas an antibody to the alpha-chain of VLA-5 was partly inhibitory. Taken together, the data suggest that FN by interacting with its receptors differentially regulates the protein synthesis of glomerular mesangial cells, promoting IL-6 secretion and inhibiting FN synthesis.
MESH: Antibodies-pharmacology; Cells,-Cultured; Fibronectins-genetics; Glomerular-Mesangium-drug-effects; Integrins-antagonists-and-inhibitors; Integrins-physiology; Oligopeptides-pharmacology; Peptide-Fragments-pharmacology; Receptors,-Fibronectin-antagonists-and-inhibitors; Receptors,-Fibronectin-physiology; RNA,-Messenger-metabolism
MESH: *Fibronectins-biosynthesis; *Fibronectins-pharmacology; *Glomerular-Mesangium-metabolism; *Interleukin-6-biosynthesis
TG: Human
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0; 0; 0; 91037-65-9
NM: integrin-alpha3beta1; Antibodies; Fibronectins; Integrins; Interleukin-6; Oligopeptides; Peptide-Fragments; Receptors,-Fibronectin; RNA,-Messenger; arginyl-glycyl-aspartyl-serine
AN: 96380587
UD: 9612
MEDLINE EXPRESS (R) 1/96-12/96 3 of 125
TI: Bcr/Abl expression stimulates integrin function in hematopoietic cell lines.
AU: Bazzoni-G; Carlesso-N; Griffin-JD; Hemler-ME
AD: Division of Tumor Virology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
SO: J-Clin-Invest. 1996 Jul 15; 98(2): 521-8
ISSN: 0021-9738
PY: 1996
LA: ENGLISH
CP: UNITED-STATES
AB: Cell adhesion to the extracellular matrix is largely mediated by adhesion molecules of the integrin family and is often diminished upon oncogenic transformation. However, we show here that the chronic myelogenous leukemia oncogene Bcr/Abl has positive effects on VLA-4 and VLA-5 integrin function. The presence of Bcr/Abl in the GM-CSF- or IL-3-dependent hematopoietic cell lines MO7e, 32D, and BaF/3 enhanced cell binding to both soluble and immobilized fibronectin. The effect was due to enhanced function of the VLA-5 integrin fibronectin receptor and not to increased surface expression. In parallel, Bcr/Abl stimulated cell adhesion to the VLA-4 integrin ligand VCAM-1. Stimulation of VLA-5 function directly correlated with induction of Bcr/Abl tyrosine kinase activity in a temperature-sensitive kinase mutant. Thus, Bcr/Abl stimulates integrin-dependent cell adhesion, by a mechanism involving increased ligand binding, with the tyrosine kinase activity of Bcr/Abl likely playing a key role. Consistent with these results, hematopoietic precursor cells from chronic myelogenous leukemia patients also showed increased adhesion to fibronectin.
MESH: Cell-Line; Fibronectins-; Fusion-Proteins,-bcr-abl-physiology; Granulocyte-Macrophage-Colony-Stimulating-Factor-pharmacology; Immunoblotting-; Interleukin-3-pharmacology; Kinetics-; Leukemia,-Experimental; Leukemia,-Megakaryocytic,-Acute; Mice-; Receptors,-Fibronectin-physiology; Receptors,-Lymphocyte-Homing-physiology; Recombinant-Proteins-biosynthesis; Recombinant-Proteins-metabolism; Time-Factors; Transfection-; Tumor-Cells,-Cultured; Vascular-Cell-Adhesion-Molecule-1-physiology
MESH: *Cell-Adhesion; *Fusion-Proteins,-bcr-abl-biosynthesis; *Hematopoietic-Stem-Cells-physiology; *Integrins-physiology
TG: Animal; Human; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: CA42368CANCI; CA66996CANCI
RN: 0; 0; 0; 0; 0; 0; 0; 0; 0; 83869-56-1
NM: integrin-alpha4beta1; Fibronectins; Fusion-Proteins,-bcr-abl; Integrins; Interleukin-3; Receptors,-Fibronectin; Receptors,-Lymphocyte-Homing; Recombinant-Proteins; Vascular-Cell-Adhesion-Molecule-1; Granulocyte-Macrophage-Colony-Stimulating-Factor
AN: 96331260
UD: 9611
SB: AIM
MEDLINE EXPRESS (R) 1/96-12/96 4 of 125
TI: HST-1/FGF-4 stimulates proliferation of megakaryocyte progenitors synergistically and promotes megakaryocyte maturation.
AU: Konishi-H; Ochiya-T; Yasuda-Y; Sakamoto-H; Muto-T; Sugimura-T; Terada-M
AD: Genetics Division, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
SO: Oncogene. 1996 Jul 4; 13(1): 9-19
ISSN: 0950-9232
PY: 1996
LA: ENGLISH
CP: ENGLAND
AB: Megakaryocyte (MK) development is dependent on the complex interaction of MK progenitors, various cytokines and stromal elements. We previously reported that an injection of replication-deficient adenovirus containing HST-1/FGF-4 cDNA (Adex1HST-1) into mice caused a twofold increase in peripheral platelet count for 30 days without any other hematological or histological abnormality. In the present study using Adex1HST-1-infected human megakaryocytic Dami cells, we demonstrated for the first time that HST-1/FGF-4 promoted MK maturation, inducing increases in DNA ploidy, cytoplasmic and membrane maturation, and platelet-like particle release. Moreover, HST-1/FGF-4 acted on megakaryocytic cells to induce secretion of IL-6 and TNF-alpha, and increased adhesion of megakaryocytic cells to human endothelial cells primarily via VLA-4 and LFA-1 molecules; both mechanisms have been shown to lead to MK maturation. We also showed that HST-1/FGF-4 stimulates the proliferation of MK progenitors not alone but synergistically with IL-3 via IL-6 and with c-mpl ligand (thrombopoietin) not via IL-6. This result supports the hypothesis of the presence of two distinct populations of MK progenitors: IL-3-dependent and Tpo-dependent. All these results suggest that HST-1/FGF-4 can regulate MK development not only as an MK potentiating factor, but also as an inducer of cytokine secretion from MK, and as a modulator of adhesive interactions with endothelial cells.
MESH: Adenoviruses,-Human-genetics; Amino-Acid-Sequence; Cell-Adhesion-drug-effects; Cell-Differentiation-drug-effects; Cell-Division-drug-effects; Cell-Line; Drug-Synergism; DNA-Replication; Endothelium,-Vascular-cytology; Fibroblast-Growth-Factor-genetics; Fibroblast-Growth-Factor-pharmacology; Genetic-Vectors-genetics; Integrins-metabolism; Interleukin-3-pharmacology; Interleukin-6-pharmacology; Interleukin-6-physiology; Lymphocyte-Function-Associated-Antigen-1-metabolism; Mice-; Mice,-Inbred-BALB-C; Molecular-Sequence-Data; Ploidies-; Proto-Oncogene-Proteins-genetics; Proto-Oncogene-Proteins-pharmacology; Receptors,-Lymphocyte-Homing-metabolism; Recombinant-Fusion-Proteins-metabolism; Recombinant-Fusion-Proteins-pharmacology; Thrombopoietin-pharmacology; Tumor-Necrosis-Factor-pharmacology; Tumor-Necrosis-Factor-secretion; Umbilical-Veins
MESH: *Fibroblast-Growth-Factor-physiology; *Megakaryocytes-cytology; *Proto-Oncogene-Proteins-physiology
TG: Animal; Comparative-Study; Human; Male; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 62031-54-3; 9014-42-0
NM: integrin-alpha4beta1; proto-oncogene-protein-kfgf; Genetic-Vectors; Integrins; Interleukin-3; Interleukin-6; Lymphocyte-Function-Associated-Antigen-1; Proto-Oncogene-Proteins; Receptors,-Lymphocyte-Homing; Recombinant-Fusion-Proteins; Tumor-Necrosis-Factor; Fibroblast-Growth-Factor; Thrombopoietin
AN: 96292222
UD: 9611
MEDLINE EXPRESS (R) 1/96-12/96 5 of 125
TI: Leukocyte activation study during occlusive arterial disease of the lower limb: effect of pentoxifylline infusion.
AU: Fossat-C; Fabre-D; Alimi-Y; Bienvenu-J; Aillaud-MF; Lenoble-M; Juhan-Vague-I; Juhan-C
AD: Laboratoire d'Hematologie, CHU Timone, Marseille, Puteaux, France.
SO: J-Cardiovasc-Pharmacol. 1995; 25 Suppl 2: S96-100
ISSN: 0160-2446
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: Granulocytes play a significant role in vascular diseases. The mechanisms of neutrophil-mediated vascular injury include their increased endothelial adhesion and activation with release of inflammatory mediators. Pentoxifylline (PTX) has a well-demonstrated ability to act on the activated neutrophils. It increases chemotaxis and decreases their adherence to endothelial cells, oxidative burst, and enzyme release. In this preliminary study, we investigated the effects of PTX on ischemia-induced changes in polymorphonuclear neutrophils (PMN) activation and cytokine release. A double-blind, randomized, placebo-controlled trial was carried out in 14 patients (age range 46-86 years) suffering from critical ischemia, as defined by the European Consensus Document, or subacute ischemia due to occlusive arterial disease of the lower limb. Femoral and antecubital venous blood samples on the side of the ischemic leg were obtained from patients immediately before (TO) and after infusion (T24) of PTX or placebo. PMN activation was evaluated by study of cell migration, beta 2 integrin expression (CD11b/ CD18), oxidative burst, and elastase release. Inflammation proteins were analyzed, such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-6 (IL-6), C-reactive protein (CRP), and fibrinogen. Before treatment, our results demonstrate an important activation in both femoral and antecubital venous blood. PMN activation markers, cytokine release, and other inflammation proteins were significantly increased compared with normal subjects. In the experimental group there was no significant difference between femoral and antecubital venous blood. Six patients received PTX infusion and seven patients were in the placebo group. The effect of PTX was evaluated after 24 h of treatment (1,200 mg). In the PTX group the following variables were improved compared with the placebo group: CD11b expression on PMNs, elastase released from PMNs, fibrinogen, CRP, TNF-alpha, and IL6 in plasma. These preliminary results should be interpreted with caution because of the small sample size. Further trials may contribute to more complete understanding.
MESH: Aged-; Aged,-80-and-over; Biological-Markers; Cell-Adhesion-drug-effects; Chemotaxis,-Leukocyte-drug-effects; Cytokines-metabolism; Double-Blind-Method; Hydrogen-Peroxide-blood; Integrins-biosynthesis; Leg-blood-supply; Leukocytes-drug-effects; Middle-Age; Neutrophils-drug-effects; Neutrophils-metabolism; Regional-Blood-Flow-drug-effects
MESH: *Arterial-Occlusive-Diseases-blood; *Leukocytes-metabolism; *Macrophage-Activation-drug-effects; *Pentoxifylline-pharmacology; *Vasodilator-Agents-pharmacology
TG: Human; Male; Support,-Non-U.S.-Gov't
PT: CLINICAL-TRIAL; JOURNAL-ARTICLE; RANDOMIZED-CONTROLLED-TRIAL
RN: 0; 0; 0; 0; 6493-05-6; 7722-84-1
NM: Biological-Markers; Cytokines; Integrins; Vasodilator-Agents; Pentoxifylline; Hydrogen-Peroxide
AN: 96234434
UD: 9611
MEDLINE EXPRESS (R) 1/96-12/96 6 of 125
TI: Cytokine regulation of proliferation and cell adhesion are correlated events in human CD34+ hemopoietic progenitors.
AU: Levesque-JP; Haylock-DN; Simmons-PJ
AD: Department of Haematology, Hanson Centre for Cancer Research, Adelaide,Australia.
SO: Blood. 1996 Aug 15; 88(4): 1168-76
ISSN: 0006-4971
PY: 1996
LA: ENGLISH
CP: UNITED-STATES
AB: Adhesive interactions with the extracellular matrix of the bone marrow (BM) stroma are of critical importance in the regulation of hematopoiesis. In part, these interactions are presumed to play an important role in retaining CD34+ hematopoietic progenitor cells (HPCs) within the BM environment, in close proximity with BM stromal cells and the cytokines they produce. Evidence of a more direct role for cell adhesion in the regulation of hematopoiesis is provided by recent data showing that adhesive interactions can also provide important costimulatory signals. We have previously shown that normal CD34+ HPCs express high levels of fibronectin (Fn) receptors very late antigen-4 (VLA-4) and VLA-5 in a low-affinity state, which do not allow HPCs to strongly adhere on immobilized Fn, and that cytokines such as interleukin-3, granulocyte-monocyte colony-stimulating factor, and stem cell factor transiently activate these receptors, providing HPCs with an adhesive phenotype on Fn. Thus, knowledge of the functional states of adhesion receptors is critical to our understanding of the physiological mechanisms responsible for the regulation of normal hematopoiesis. Herein, we show that combinations of cytokines that synergize to stimulate the proliferation of CD34+ HPCs result in additive stimulation of the adhesion of these cells to Fn. Thus, the activation level of Fn receptors expressed by normal CD34+ HPCs is highly correlated with their proliferative state, suggesting a functional link between these two events. Therefore, we propose a 2-step model with an initial activation of VLA-4 and VLA-5 generated by cytokine receptors that is followed by a secondary signal resulting from Fn binding to VLA-4 and VLA-5, which may cooperate with those generated by cytokine receptors.
MESH: Adult-; Bone-Marrow-cytology; Cell-Adhesion; Cell-Division; Cells,-Cultured; Fibronectins-physiology; Receptors,-Cytokine
MESH: *Cell-Adhesion-Molecules-physiology; *Cytokines-physiology; *Hematopoietic-Stem-Cells-cytology; *Integrins-physiology; *Receptors,-Fibronectin-physiology; *Receptors,-Lymphocyte-Homing-physiology
TG: Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0; 0
NM: integrin-alpha4beta1; Cell-Adhesion-Molecules; Cytokines; Fibronectins; Integrins; Receptors,-Cytokine; Receptors,-Fibronectin; Receptors,-Lymphocyte-Homing
AN: 96329548
UD: 9611
SB: AIM
MEDLINE EXPRESS (R) 1/96-12/96 7 of 125
TI: Comparative immunophenotypic analysis of human mast cells, blood basophils and monocytes.
AU: Agis-H; Fureder-W; Bankl-HC; Kundi-M; Sperr-WR; Willheim-M; Boltz-Nitulescu-G; Butterfield-JH; Kishi-K; Lechner-K; Valent-P
AD: Department of Internal Medicine I, University of Vienna, Austria.
SO: Immunology. 1996 Apr; 87(4): 535-43
ISSN: 0019-2805
PY: 1996
LA: ENGLISH
CP: ENGLAND
AB: Mast cells (MC), blood basophils (Ba) and monocytes (Mo) are of haemopoietic origin. Lineage-relationships and transdifferentiation between MC and Mo, or MC and Ba, have been considered, based on common expression of antigens. In this study, comparative phenotypic analyses on MC, Ba and Mo and on respective cell lines were performed using monoclonal antibodies (mAb) to previously defined and novel CD antigens (CD1-130). By cluster analysis, the overall (all 130 CD) phenotypic relationships (given as similarity indices, SI), between primary cells (MC, Ba and Mo) and corresponding cell lines (HMC-1, KU-812, U937) were 0.716, 0.779 and 0.757, respectively. When primary cells were compared, lower SI values were found (MC versus Ba, 0.509; MC versus Mo, 0.625; Mo versus Ba, 0.698). More distant relationships were found between MC versus Ba and MC versus Mo, compared with Ba versus Mo, for adhesion receptor (R)-, complement R- and cytokine R profiles. Analysis of cytokine R revealed most significant dissimilarities between MC versus Ba and MC versus Mo (SI < 0.2). Moreover, in contrast to other CD subgroups and other lineages, MC and HMC-1 differed from each other in cytokine R expression (SI = 0.286). Cytokine R detectable on HMC-1 but not MC were granulocyte-macrophage colony-stimulating factor (GM-CSFR)alpha(CD116), CD40, Apo-1/FAS(CD95) and gp130(CD130). Cytokine R detectable on Ba but not MC, were interleukin-3 (IL-3)R alpha(CD123), IL-1RII(CD121b), IL-2R alpha(CD25) and CD40. In summary, MC, Ba and Mo display a unique CD profile with MC being the most distantly related cell. The most significant mismatch within a given lineage is the loss of cytokine R on mature MC as compared with normal myeloid progenitors and HMC-1 cells.
MESH: Basophils-immunology; Cell-Culture; Fluorescent-Antibody-Technique; Immunophenotyping-; Integrins-analysis; Mast-Cells-immunology; Monocytes-immunology; Receptors,-Cytokine-analysis; Receptors,-Fc-analysis; Receptors,-Immunologic-analysis
MESH: *Antigens,-CD-analysis; *Basophils-classification; *Mast-Cells-classification; *Monocytes-classification
TG: Comparative-Study; Female; Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0
NM: Antigens,-CD; Integrins; Receptors,-Cytokine; Receptors,-Fc; Receptors,-Immunologic
AN: 96256135
UD: 9610
MEDLINE EXPRESS (R) 1/96-12/96 8 of 125
TI: Inactivation of the integrin beta 6 subunit gene reveals a role of epithelial integrins in regulating inflammation in the lung and skin.
AU: Huang-XZ; Wu-JF; Cass-D; Erle-DJ; Corry-D; Young-SG; Farese-RV Jr; Sheppard-D
AD: Lung Biology Center, University of California, San Francisco 94143, USA.
SO: J-Cell-Biol. 1996 May; 133(4): 921-8
ISSN: 0021-9525
PY: 1996
LA: ENGLISH
CP: UNITED-STATES
AB: The integrin alpha v beta 6 is only expressed in epithelial cells. In healthy adult epithelia, this receptor is barely detectable, but expression is rapidly induced following epithelial injury. Mice homozygous for a null mutation in the gene encoding the beta 6 subunit had juvenile baldness associated with infiltration of macrophages into the skin, and accumulated activated lymphocytes around conducting airways in the lungs. Beta 6-/- mice also demonstrated airway hyperresponsiveness to acetylcholine, a hallmark feature of asthma. These results suggest that the epithelial integrin alpha v beta 6 participates in the modulation of epithelial inflammation. Genetic or acquired alterations in this integrin could thus contribute to the development of inflammatory diseases of epithelial organs, such as the lungs and skin.
MESH: Alopecia-genetics; Alopecia-immunology; Base-Sequence; Cell-Line; Cell-Movement; Cells,-Cultured; DNA-Primers; Guinea-Pigs; Integrins-genetics; Interferon-Type-II-biosynthesis; Interleukin-4-biosynthesis; Keratinocytes-cytology; Keratinocytes-immunology; Lung-cytology; Lymphocyte-Transformation; Lymphocytes-immunology; Macrophages-immunology; Mice-; Mice,-Inbred-C57BL; Molecular-Sequence-Data; Mutation-; Skin-cytology; Stem-Cells-cytology; Stem-Cells-immunology
MESH: *Inflammation-Mediators-immunology; *Integrins-immunology; *Lung-immunology; *Skin-immunology
TG: Animal; Female; Human; Male; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: HLA133259HLNHLBI; HL47412HLNHLBI; HL53949HLNHLBI
RN: 0; 0; 0; 0; 0; 82115-62-6
NM: integrin-alphavbeta6; DNA-Primers; Inflammation-Mediators; Integrins; Interleukin-4; Interferon-Type-II
AN: 96234678
UD: 9610
MEDLINE EXPRESS (R) 1/96-12/96 9 of 125
TI: Integrin signaling to NF-kappa B in monocytic leukemia cells is blocked by activated oncogenes.
AU: Rosales-C; Juliano-R
AD: Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, 27599, USA.
SO: Cancer-Res. 1996 May 15; 56(10): 2302-5
ISSN: 0008-5472
PY: 1996
LA: ENGLISH
CP: UNITED-STATES
AB: Integrin-mediated signals play an important but poorly understood role in regulating the growth and behavior of tumor cells. In monocytes and monocytic leukemia cells, integrin-mediated adhesion results in a strong induction of a set of immediate early genes that are characteristic of monocytic differentiation and contain consensus NF-kappa B elements in their 5' regulatory regions. To investigate the role of integrin signaling in control of differentiation in a human monocytic leukemia cell line, THP-1 cells were transiently transfected with an NF-kappa B driven CAT reporter gene. Adhesion to fibronectin or cross-linking of beta1 integrins resulted in an NF-kappa B-dependent induction of CAT activity. To evaluate whether integrin signaling in this system intersects with the Ras signal transduction cascade, THP-1 cells were cotransfected with the NF-kappa B reporter and with plasmids that direct the synthesis of normal or mutant forms of Ras or Raf. We found that Ras or Raf dominant negative mutants did not inhibit integrin-mediated activation of the NF-kappa B-driven reporter. However, cotransfection with activated Ras, or with several other cytoplasmic oncogenes, blocked this process. This suggests that in monocytic leukemia cells, an antagonism exists between the mitogenic signals provided by oncogenes and the signals generated by integrin ligation. This antagonism may play an important role in regulating the balance between proliferation and differentiation in monocytic leukemias.
MESH: Cell-Adhesion; Cell-Differentiation-genetics; Cell-Division-genetics; Chloramphenicol-Acetyltransferase-biosynthesis; Chloramphenicol-Acetyltransferase-genetics; Fibronectins-metabolism; Genes,-ras; Genes,-Reporter; Interleukin-8-genetics; Monocytes-pathology; Protein-Serine-Threonine-Kinases-genetics; Proto-Oncogene-Proteins-genetics; Transfection-; Tumor-Cells,-Cultured
MESH: *Gene-Expression-Regulation,-Leukemic; *Genes,-Immediate-Early; *Integrins-physiology; *Leukemia,-Monocytic,-Acute-pathology; *Neoplasm-Proteins-physiology; *NF-kappa-B-metabolism; *Oncogenes-; *Protein-Serine-Threonine-Kinases-physiology; *Proto-Oncogene-Protein-p21ras-physiology; *Proto-Oncogene-Proteins-physiology; *Signal-Transduction-genetics
TG: Human; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: GM26165GMNIGMS; NHLBI45100
RN: EC 2.3.1.28; EC 2.7.10; EC 2.7.10.-; 0; 0; 0; 0; 0; 0; 0
NM: Chloramphenicol-Acetyltransferase; Protein-Serine-Threonine-Kinases; proto-oncogene-protein-mil; Fibronectins; Integrins; Interleukin-8; Neoplasm-Proteins; NF-kappa-B; Proto-Oncogene-Protein-p21(ras); Proto-Oncogene-Proteins
AN: 96200311
UD: 9608
MEDLINE EXPRESS (R) 1/96-12/96 10 of 125
TI: The role of cytokines, adhesion molecules, and chemokines in interleukin-2-induced lymphocytic infiltration in C57BL/6 mice.
AU: Anderson-JA; Lentsch-AB; Hadjiminas-DJ; Miller-FN; Martin-AW; Nakagawa-K; Edwards-MJ
AD: Department of Surgery, J. Graham Brown Cancer Center, University of Louisville School of Medicine, Kentucky 40292, USA.
SO: J-Clin-Invest. 1996 Apr 15; 97(8): 1952-9
ISSN: 0021-9738
PY: 1996
LA: ENGLISH
CP: UNITED-STATES
AB: IL-2 mediates the regression of certain malignancies, but clinical use is limited because of associated toxicities, including parenchymal lymphocytic infiltration with multiple organ failure. Secondarily induced cytokines are important mediators of IL-2 toxicity and IL-2-induced lymphocyte-endothelial adherence and trafficking. The recently discovered C-C chemokines, RANTES (regulated on activation, normal T expressed and secreted) and macrophage inflammatory protein-1alpha, have also been implicated in lymphocytic migration. We hypothesized that IL-2 alters cytokine, C-C chemokine, and adhesion molecule expression in association with parenchymal lymphocytic infiltration. C57BL/6 mice were injected with 3x10(5) IU of IL-2 or 0.1 ml of 5% dextrose intraperitoneally every 8 h for 6 d, then killed. IL-2 induced massive lymphocytic infiltration in the liver and lung and moderate infiltration in the kidney in association with organ edema and dysfunction. Immunostaining showed increased intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression in association with this organ-specific lymphocytic infiltration. Flow cytometry showed increased expression of the corresponding ligands (lymphocyte function-associated antigen-1 and very late antigen-4) on splenocytes. IL-2 increased TNF-alpha mRNA and protein expression in the liver. Organs infiltrated by lymphocytes had increased TNF-alpha mRNA, whereas RANTES mRNA was increased in all organs, regardless of lymphocytic infiltration. IL-2 toxicity involves organ-specific TNF-alpha and RANTES production with increased ICAM-1 and VCAM-1 expression as potential mechanisms facilitating lymphocytic infiltration and organ dysfunction.
MESH: Base-Sequence; DNA-Primers; Integrins-biosynthesis; Intercellular-Adhesion-Molecule-1-biosynthesis; Kidney-immunology; Liver-immunology; Lung-immunology; Lymphocytes-drug-effects; Mice-; Mice,-Inbred-C57BL; Molecular-Sequence-Data; Myocardium-immunology; Organ-Specificity; Polymerase-Chain-Reaction; Receptors,-Lymphocyte-Homing-biosynthesis; Recombinant-Proteins-pharmacology; RANTES-biosynthesis; Tumor-Necrosis-Factor-biosynthesis; Vascular-Cell-Adhesion-Molecule-1-biosynthesis
MESH: *Cell-Adhesion-Molecules-biosynthesis; *Chemokines-biosynthesis; *Cytokines-biosynthesis; *Gene-Expression-drug-effects; *Interleukin-2-pharmacology; *Lymphocytes-immunology
TG: Animal; Comparative-Study; Female; Human; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: CA57527CANCI
RN: 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 126547-89-5
NM: integrin-alpha4beta1; Cell-Adhesion-Molecules; Chemokines; Cytokines; DNA-Primers; Integrins; Interleukin-2; Receptors,-Lymphocyte-Homing; Recombinant-Proteins; RANTES; Tumor-Necrosis-Factor; Vascular-Cell-Adhesion-Molecule-1; Intercellular-Adhesion-Molecule-1
AN: 96194696
UD: 9608
SB: AIM
MEDLINE EXPRESS (R) 1/96-12/96 11 of 125
TI: VLA-5-mediated interaction with fibronectin induces cytokine production by human chondrocytes.
AU: Yonezawa-I; Kato-K; Yagita-H; Yamauchi-Y; Okumura-K
AD: Department of Orthopedic Surgery, Juntendo University School of Medicine, Tokyo, Japan.
SO: Biochem-Biophys-Res-Commun. 1996 Feb 6; 219(1): 261-5
ISSN: 0006-291X
PY: 1996
LA: ENGLISH
CP: UNITED-STATES
AB: Adhesion molecules of the integrin family, including very late activation antigens (VLA), have been implicated in various cellular functions. In this study, we investigated the contribution of integrin-mediated interaction with ECM proteins to the cytokine gene expression in human chondrocytes. Human articular chondrocytes expressed VLA-1, -2, -3 and -5 on the cell surface, and could adhere to various ECM proteins, especially to fibronectin (FN). Furthermore, the production of GM-CSF and IL-6 was potently induced by culturing chondrocytes on immobilized FN. This stimulative effect of FN was completely inhibited by an anti-integrin alpha 5 chain mAb, as well as by anti-integrin beta 1 chain mAbs. These results indicate an important role of the VLA-5-mediated interaction with FN in regulating inflammatory cytokine production by human articular chondrocytes.
MESH: Antibodies,-Monoclonal-pharmacology; Cartilage,-Articular-metabolism; Cell-Adhesion; Cells,-Cultured; Collagen-pharmacology; Extracellular-Matrix-Proteins-pharmacology; Gene-Expression; Granulocyte-Macrophage-Colony-Stimulating-Factor-biosynthesis; Integrins-analysis; Interleukin-6-biosynthesis; Macromolecular-Systems; Mice-; Rats-; Receptors,-Fibronectin-immunology; RNA,-Messenger-analysis; RNA,-Messenger-biosynthesis
MESH: *Cartilage,-Articular-immunology; *Cytokines-biosynthesis; *Fibronectins-pharmacology; *Integrins-biosynthesis; *Receptors,-Fibronectin-physiology
TG: Animal; Comparative-Study; Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0; 0; 0; 83869-56-1; 9007-34-5
NM: Antibodies,-Monoclonal; Cytokines; Extracellular-Matrix-Proteins; Fibronectins; Integrins; Interleukin-6; Macromolecular-Systems; Receptors,-Fibronectin; RNA,-Messenger; Granulocyte-Macrophage-Colony-Stimulating-Factor; Collagen
AN: 96190703
UD: 9608
MEDLINE EXPRESS (R) 1/96-12/96 12 of 125
TI: Influence of cytokine stimulation (granulocyte macrophage-colony stimulating factor, interleukin-3 and transforming growth factor-beta-1) on adhesion molecule expression in normal human bone marrow fibroblasts.
AU: Schmitz-B; Park-IA; Kaufmann-R; Thiele-J; Fischer-R
AD: Institute of Pathology, University of Cologne, Germany.
SO: Acta-Haematol. 1995; 94(4): 173-81
ISSN: 0001-5792
PY: 1995
LA: ENGLISH
CP: SWITZERLAND
AB: Interactions between stromal cells or extracellular matrix and hematopoietic cells are important factors for the very complex processes associated with differentiation and maturation in the bone marrow. To elucidate these multifold processes, the expression pattern of various adhesion molecules was studied on enriched fibroblastic populations derived from healthy volunteers. CD44 (homing cell adhesion molecule) and very late activation antigen beta 1 (VLA beta 1; CD29) could be demonstrated on almost all fibroblasts without an alteration following cytokine stimulation. On the other hand, VLA-2 (CDw49b), VLA-3 (CDw49c), VLA-4 (CDw49d), VLA-5 (CDw49e), intercellular adhesion molecule-1 (ICAM-1; CD54) and vascular cell adhesion molecule-1 (VCAM-1; CD106) were only represented by certain cell fractions. In our studies recombinant human granulocyte macrophage-colony stimulating factor failed to alter the expression pattern of these adhesion molecules, whereas recombinant human interleukin-3 (rhIL-3 showed a tendency for downregulation of the VLA antigens except for VLA beta 1. However, recombinant human transforming growth factor-beta 1 (rhTGF beta 1) exerted a reducing effect on the expression of VLA-3 and induced an increase in the VLA-5-positive fraction. In the immunoglobin class VCAM-1 revealed a decrease staining capacity after stimulation with rhTGF beta 1 and rhIL-3. Contrary to this finding, the presentation of ICAM-1 increased after administration of these mediators.
MESH: Antigens,-CD29-metabolism; Antigens,-CD44-metabolism; Bone-Marrow-metabolism; Cells,-Cultured; Immunohistochemistry-; Integrins-metabolism; Intercellular-Adhesion-Molecule-1-metabolism; Receptors,-Fibronectin-metabolism; Receptors,-Lymphocyte-Homing-metabolism
MESH: *Bone-Marrow-cytology; *Cell-Adhesion-Molecules-metabolism; *Fibroblasts-metabolism; *Granulocyte-Macrophage-Colony-Stimulating-Factor-pharmacology; *Interleukin-3-pharmacology; *Transforming-Growth-Factor-beta-pharmacology
TG: Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 126547-89-5; 83869-56-1
NM: collagen-receptor; integrin-alpha3beta1; integrin-alpha4beta1; Antigens,-CD29; Antigens,-CD44; Cell-Adhesion-Molecules; Integrins; Interleukin-3; Receptors,-Fibronectin; Receptors,-Lymphocyte-Homing; Transforming-Growth-Factor-beta; Intercellular-Adhesion-Molecule-1; Granulocyte-Macrophage-Colony-Stimulating-Factor
AN: 96190618
UD: 9608
MEDLINE EXPRESS (R) 1/96-12/96 13 of 125
TI: IL-4 and TNF-alpha induce changes in integrin expression and adhesive properties and decrease the lung-colonizing potential of HT-29 colon carcinoma cells.
AU: Herzberg-F; Schoning-M; Schirner-M; Topp-M; Thiel-E; Kreuser-ED
AD: Department of Hematology and Oncology, University Medical Center Benjamin Franklin, Free University of Berlin, Germany. herzberg@fub46.zedat.fu-berlin.de.
SO: Clin-Exp-Metastasis. 1996 Mar; 14(2): 165-75
ISSN: 0262-0898
PY: 1996
LA: ENGLISH
CP: ENGLAND
AB: The colon carcinoma cell line HT-29 was used to explore the potential of interleukin-4 (IL-4) and tumor necrosis factor alpha (TNF-alpha) to modify integrin expression and adhesive functions of tumor cells in vitro and to examine corresponding metastatic effects in vivo. Preincubation of HT-29 cells with 100 U/ml of IL-4 for 48 h downregulated the surface expression of the integrin subunits alpha 2, alpha 3, beta 1 and beta 4 after 48 h, whereas the alpha 1 subunit was upregulated. In contrast, 100 U/ml to TNF-alpha selectively upmodulated the expression of alpha v. Attachment to fibronectin of cells treated with IL-4 increased twofold (63.5% vs 32.4%). Adhesion to fibronectin (54.0% vs 32.4%) and vitronectin (37.9% vs 16.4%) was elevated in the case of TNF-alpha stimulation. Using an experimental metastasis model, HT-29 cells showed a significant reduction of their lung-colonizing potential in nude mice when preincubated with IL-4 for 48 h before intravenous injection. The decrease also observed for TNF-alpha-treated cells was less pronounced. The data indicate that the cytokines IL-4 and TNF-alpha can act as direct regulators of adhesive mechanisms of tumor cells bearing adequate receptors, thus influencing lung-colony formation.
MESH: Cell-Adhesion-drug-effects; Cell-Division-drug-effects; Fibronectins-metabolism; Gene-Expression; Integrins-genetics; Lung-Neoplasms-secondary; Mice-; Mice,-Nude; RNA,-Messenger-genetics; RNA,-Neoplasm-genetics
MESH: *Carcinoma-pathology; *Colonic-Neoplasms-pathology; *Integrins-metabolism; *Interleukin-4-pharmacology; *Tumor-Necrosis-Factor-pharmacology
TG: Animal; Female; Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0
NM: Fibronectins; Integrins; Interleukin-4; RNA,-Messenger; RNA,-Neoplasm; Tumor-Necrosis-Factor
AN: 96190825
UD: 9607
MEDLINE EXPRESS (R) 1/96-12/96 14 of 125
TI: Role of Rho in chemoattractant-activated leukocyte adhesion through integrins.
AU: Laudanna-C; Campbell-JJ; Butcher-EC
AD: Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University, CA 94305, USA.
SO: Science. 1996 Feb 16; 271(5251): 981-3
ISSN: 0036-8075
PY: 1996
LA: ENGLISH
CP: UNITED-STATES
AB: Heterotrimeric guanine nucleotide binding protein (G protein)-linked receptors of the chemoattractant subfamily can trigger adhesion through leukocyte integrins, and in this role they are thought to regulate immune cell-cell interactions and trafficking. In lymphoid cells transfected with formyl peptide or interleukin-8 receptors, agonist stimulation activated nucleotide exchange on the small guanosine triphosphate-binding protein RhoA in seconds. Inactivation of Rho by C3 transferase exoenzyme blocked agonist-induced lymphocyte alpha4beta1 adhesion to vascular cell adhesion molecule-1 and neutrophil beta2 integrin adhesion to fibrinogen. These findings suggest that Rho participates in signaling from chemoattractant receptors to trigger rapid adhesion in leukocytes.
MESH: Amino-Acid-Sequence; Antigens,-CD-genetics; Cells,-Cultured; G-Proteins-metabolism; Guanosine-Diphosphate-metabolism; Guanosine-5'-O-3-Thiotriphosphate-metabolism; Interleukin-8-pharmacology; Mice-; Molecular-Sequence-Data; N-Formylmethionine-Leucyl-Phenylalanine-pharmacology; Receptors,-Immunologic-genetics; Receptors,-Interleukin-genetics; Receptors,-Peptide-genetics; Signal-Transduction; Tetradecanoylphorbol-Acetate-pharmacology; Transfection-
MESH: *B-Lymphocytes-physiology; *Cell-Adhesion; *Chemotactic-Factors-pharmacology; *G-Proteins-physiology; *Integrins-physiology; *Receptors,-Lymphocyte-Homing-physiology; *Vascular-Cell-Adhesion-Molecule-1-physiology
TG: Animal; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-Non-P.H.S.; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: 5T32CA09302CANCI; 1F32AI08930AINIAID
RN: 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 146-91-8; 16561-29-8; 37589-80-3; 59880-97-6
NM: chemotactic-peptide-receptor; integrin-alpha4beta1; interleukin-8-receptor; rhoA-p21-protein; Antigens,-CD; Chemotactic-Factors; G-Proteins; Integrins; Interleukin-8; Receptors,-Immunologic; Receptors,-Interleukin; Receptors,-Lymphocyte-Homing; Receptors,-Peptide; Vascular-Cell-Adhesion-Molecule-1; Guanosine-Diphosphate; Tetradecanoylphorbol-Acetate; Guanosine-5'-O-(3-Thiotriphosphate); N-Formylmethionine-Leucyl-Phenylalanine
AN: 96172356
UD: 9605
MEDLINE EXPRESS (R) 1/96-12/96 15 of 125
TI: Isolation and characterization of cell lines with genetically distinct mutations downstream of protein kinase C that result in defective activation-dependent regulation of T cell integrin function.
AU: Mobley-JL; Ennis-E; Shimizu-Y
AD: Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis 55455, USA.
SO: J-Immunol. 1996 Feb 1; 156(3): 948-56
ISSN: 0022-1767
PY: 1996
LA: ENGLISH
CP: UNITED-STATES
AB: beta 1-integrins expressed on resting T cells support only minimal adhesion to integrin ligands. T cell activation through multiple stimuli, including phorbol ester treatment and Ab cross-linking of the CD3/TCR complex, results in a rapid and transient switch in integrin function from low to high avidity binding. The exact nature of the intracellular signals involved in this avidity switch remain poorly defined, but the ability of phorbol esters to induce such up-regulation implicates a role for protein kinase C (PKC). We have used a genetic approach to identify factors other than PKC that regulate activation-dependent beta 1-integrin function on T cells. We isolated mutants of the Jurkat T cell line that express beta 1- and beta 2-integrins but do not exhibit increased integrin activity in response to PMA stimulation or CD3 cross-linking. PKC activity appears to be normal in the mutants. One mutation is associated with an altered form of the mitogen-activated protein kinase ERK1 and an inability to produce IL-2. Another mutant with defective integrin function has IL-2 production intact. Complementation analysis verified that these two types of mutants are genetically distinct. Thus, two mutations downstream of PKC have been identified that alter the process of integrin regulation without affecting T cell viability or proliferative capacity. These mutants represent novel reagents for the identification of integrin regulatory factors and indicate possible sites of pharmacologic intervention that could prevent integrin-dependent migration and localization in the process of inflammation, while leaving other T cell functions intact.
MESH: Antigens,-CD18-genetics; Antigens,-CD29-genetics; Cell-Adhesion-genetics; Cell-Separation; Gene-Expression-Regulation,-Neoplastic-immunology; Genetic-Complementation-Test; Integrins-biosynthesis; Integrins-physiology; Interleukin-2-biosynthesis; Interleukin-2-genetics; Lymphoma,-T-Cell-genetics; Protein-Kinase-C-deficiency; Protein-Kinase-C-physiology; Protein-Kinases-genetics; Tumor-Cells,-Cultured
MESH: *Gene-Expression-Regulation,-Neoplastic; *Integrins-genetics; *Lymphocyte-Transformation-genetics; *Lymphoma,-T-Cell-enzymology; *Mutation-; *Protein-Kinase-C-genetics
TG: Human; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: AI31126AINIAID
RN: EC 2.7.1.-; EC 2.7.1.37; 0; 0; 0; 0
NM: Protein-Kinase-C; Protein-Kinases; Antigens,-CD18; Antigens,-CD29; Integrins; Interleukin-2
AN: 96144313
UD: 9605
SB: AIM
MEDLINE EXPRESS (R) 1/96-12/96 16 of 125
TI: Lymphocyte adhesion and transendothelial migration in the central nervous system: the role of LFA-1, ICAM-1, VLA-4 and VCAM-1. off
AU: Greenwood-J; Wang-Y; Calder-VL
AD: Department of Clinical Ophthalmology, University College London, UK.
SO: Immunology. 1995 Nov; 86(3): 408-15
ISSN: 0019-2805
PY: 1995
LA: ENGLISH
CP: ENGLAND
AB: Lymphocyte adhesion to and migration across endothelial cell (EC) monolayers, derived from the rat blood-retinal barrier (BRB), were measured in vitro. The binding of concanavalin A (Con A)-activated peripheral lymph node lymphocytes and the migration of CD4+ T-cell lines could be significantly increased by treating the EC with interleukin-1 beta (IL-1 beta). To determine the role of various adhesion molecules during the processes of lymphocyte binding and transmonolayer migration (diapedesis), lymphocytes were treated with monoclonal antibody (mAb) specific for CD11a (alpha L subunit of leucocyte functional antigen-1; LFA-1), CD18 (beta 2 subunit of leucam family) and CD49d (alpha 4 subunit of very late activation antigen-4; VLA-4) and EC with mAb specific for CD54 (intercellular adhesion molecule-1; ICAM-1) and CD106 (vascular cell adhesion molecule-1; VCAM-1). Binding of the highly adhesive but non-migratory Con A-activated lymphocytes was inhibited by mAb to CD11a (reduced to 73% and 65% of control lymphocyte adhesion) and CD18 (42% and 54%) on non-activated and IL-1 beta-treated EC, respectively, but not by mAb to ICAM-1 or VCAM-1. Diapedesis of the highly migratory T-cell line lymphocytes was also blocked by antibodies to CD11a (reduced to 11% and 10% of control T-cell migration), CD18 (29% and 43%) but in addition was also inhibited by anti-ICAM-1 (17% and 53%) on non-activated and IL-1 beta treated EC, respectively. Both anti-VLA-4 and anti-VCAM-1 were also effective in producing a smaller reduction in migration, but only on IL-1 beta activated EC (66% and 58% of control migration, respectively). These studies indicate that lymphocyte adhesion to central nervous system (CNS) vascular EC is largely dependent on LFA-1 but not through its interaction with ICAM-1. In contrast, lymphocyte diapedesis is mostly supported through the LFA-1/ICAM-1 pairing, with a small proportion being mediated by VLA-4/VCAM-1 on IL-1 beta-activated EC. This latter pathway, however, also appears to be dependent on LFA-1 interacting with the EC.
MESH: Antibodies,-Blocking-pharmacology; Cell-Adhesion-physiology; Cell-Movement-physiology; Endothelium-cytology; Flow-Cytometry; Immunologic-Techniques; Integrins-physiology; Intercellular-Adhesion-Molecule-1-physiology; Lymphocyte-Function-Associated-Antigen-1-physiology; Rats-; Rats,-Inbred-Strains; Receptors,-Lymphocyte-Homing-physiology; Vascular-Cell-Adhesion-Molecule-1-physiology
MESH: *Blood-Retinal-Barrier-physiology; *Cell-Adhesion-Molecules-physiology; *Lymphocytes-physiology
TG: Animal; Female
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0; 126547-89-5
NM: integrin-alpha4beta1; Antibodies,-Blocking; Cell-Adhesion-Molecules; Integrins; Lymphocyte-Function-Associated-Antigen-1; Receptors,-Lymphocyte-Homing; Vascular-Cell-Adhesion-Molecule-1; Intercellular-Adhesion-Molecule-1
AN: 96148607
UD: 9604
MEDLINE EXPRESS (R) 1/96-12/96 17 of 125
TI: Human intestinal intraepithelial lymphocytes bind to mucosal mesenchymal cells through VLA4 and CD11A.
AU: Ebert-EC; Roberts-AI
AD: Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, New Brunswick 08903-0019, USA.
SO: Cell-Immunol. 1996 Jan 10; 167(1): 108-14
ISSN: 0008-8749
PY: 1996
LA: ENGLISH
CP: UNITED-STATES
AB: Human intestinal intraepithelial lymphocytes (IEL), predominantly CD8+ T lymphocytes, are uniquely situated at the basolateral surfaces of epithelial cells in contact with the myofibroblasts that comprise the basement membrane. Since mesenchymal cells may anchor IEL in this location and may also serve as antigen-presenting cells, the mechanism of binding to IEL was investigated. Lymphocytes were radiolabeled with [51Cr] sodium chromate, cocultured with mesenchymal cell monolayers, and the nonadherent lymphocytes removed by washes. Those adherent to the monolayers were counted by measuring the amount of radiolabel retained in the well. A large fraction of IL-2-activated IEL bound to KD (lip fibroblast), HISM (jejunal smooth muscle), and JF (jejunal fibroblast) cell lines after a 2-hr incubation: 33 +/- 11, 37 +/-14, and 48 +/- 15%, respectively. When monoclonal antibodies directed at the alpha chains of the very late activation antigens (CD49) were added alone or combined with anti CD11a to assays measuring IEL binding to KD or JF monolayers, the greatest inhibition (33 to 38%) occurred with anti-alpha 4 combined with anti-CD11a. The majority of IEL expressed alpha 1 and alpha 4 before and after a 3-day culture with IL-2, with no change in surface density. VCAM-1, a binding partner to alpha 4, was not expressed on KD or JF cells, and anti-VCAM antibody had no effect on binding. In summary, alpha 4 and CD11a on IEL mediate binding to mesenchymal cells.
MESH: Cell-Adhesion; Cell-Line; Interleukin-2-pharmacology; Intestinal-Mucosa-immunology; Lymphocyte-Transformation; Vascular-Cell-Adhesion-Molecule-1-physiology
MESH: *Integrins-physiology; *Intestinal-Mucosa-cytology; *Lymphocyte-Function-Associated-Antigen-1-physiology; *Lymphocytes-physiology; *Receptors,-Lymphocyte-Homing-physiology
TG: Human; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: DK42166DKNIDDK
RN: 0; 0; 0; 0; 0; 0
NM: integrin-alpha4beta1; Integrins; Interleukin-2; Lymphocyte-Function-Associated-Antigen-1; Receptors,-Lymphocyte-Homing; Vascular-Cell-Adhesion-Molecule-1
AN: 96139357
UD: 9604
MEDLINE EXPRESS (R) 1/96-12/96 18 of 125
TI: VLA-6 (CDw49f) is an important adhesion molecule in NK cell-mediated cytotoxicity following autologous or allogeneic bone marrow transplantation.
AU: Lowdell-MW; Shamim-F; Hamon-M; Macdonald-ID; Prentice-HG
AD: Department of Haematology, Royal Free Hospital School of Medicine, London, UK.
SO: Exp-Hematol. 1995 Dec; 23(14): 1530-4
ISSN: 0301-472X
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: Graft-vs.-leukemia (GVL) is postulated to be the principal mechanism responsible for continued remission after allogeneic bone marrow transplantation (BMT). The specific cytotoxic effectors mediating this effect are as yet undefined, but the major histocompatibility complex (MHC)-nonrestricted lysis of tumor cell lines by natural killer (NK) and lymphokine-activated killer (LAK) cells from recipients of allogeneic BMTs has been proposed as an in vitro correlate of GVL. In vitro culture or treatment in vivo with interleukin-2 (IL-2) is associated with enhanced NK cytotoxicity and lysis of NK-resistant targets (LAK cytotoxicity). NK, LAK, and cytotoxic T lymphocytes (CTL) have cytotoxic properties against autologous and allogeneic leukemic targets. These immune effector cells require receptor-ligand interaction for target recognition and adhesion via specific molecules such as integrins, a group of heterodimeric transmembrane glycoproteins. The integrins include the very late activation (VLA) subfamily, which all share the same beta 1 subunit but have distinct chains. VLA-6 (CDw49f) has been identified on NK cells and binds to laminin, a basement membrane protein found on malignant tumor cells but not normal cells. Monoclonal antibodies (mAbs) to laminin have been found to inhibit in vitro cytotoxicity of the tumor cell line K562, suggesting an important role for VLA-6 in this interaction. The specific aim of this study was to investigate the role of VLA-6 in the interactions of the tumor cell lines K562 and Daudi with peripheral blood lymphocytes (PBL) acting as effectors in cell-mediated cytotoxicity from normal volunteers, patients recovering from chemotherapy, and patients recovering from autologous or allogeneic BMT. In over 96% of assays, incubation of effector cells with anti-CDw49f mAbs led to detectable inhibition of NK and LAK cell-mediated cytotoxicity. More notably, the degree of anti-VLA6-induced suppression of LAK activity was significantly greater in the normal donors than in any of the patient groups, despite a significantly lower incidence of expression of VLA-6 on NK cells from controls than from patients. This implies a reduced role for this adhesion molecule in LAK activity following some form of in vivo stimulation. This hypothesis is supported by the observation that addition of exogenous IL-2 to the cultures ameliorated the effect of VLA-6 blockade, although the incidence and level of VLA-6 expression was unchanged by IL-2. In contrast, VLA-6 blocking led to a greater reduction in NK activity of BMT recipients than of normal donors, demonstrating that the VLA-6 adhesion pathway is important in this group of patients. These results indicate that the VLA-6-laminin interaction is important in normal NK-target interaction but may play a less significant role in the innate cytotoxic response post-BMT, perhaps reflecting subtle differences in the subsets of NK cells present in BMT recipients compared with normal donors.
MESH: Antibodies,-Monoclonal-pharmacology; Flow-Cytometry; Fluorescent-Antibody-Technique; Graft-vs-Host-Reaction; Killer-Cells,-Lymphokine-Activated-immunology; Laminin-immunology; Laminin-metabolism; Leukemia-therapy; Lymphocytes-immunology; Transplantation,-Autologous; Transplantation,-Homologous; Tumor-Cells,-Cultured
MESH: *Bone-Marrow-Transplantation-immunology; *Cytotoxicity,-Immunologic; *Integrins-immunology; *Killer-Cells,-Natural-immunology; *Leukemia-immunology; *Receptors,-Laminin-immunology
TG: Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0
NM: integrin-alpha6beta1; Antibodies,-Monoclonal; Integrins; Laminin; Receptors,-Laminin
AN: 96130286
UD: 9604
MEDLINE EXPRESS (R) 1/96-12/96 19 of 125
TI: Costimulation of CD3/TcR complex with either integrin or nonintegrin ligands protects CD4+ allergen-specific T-cell clones from programmed cell death.
AU: Agea-E; Bistoni-O; Bini-P; Migliorati-G; Nicoletti-I; Bassotti-G; Riccardi-C; Bertotto-A; Spinozzi-F
AD: Department of Internal Medicine, University of Perugia, Italy.
SO: Allergy. 1995 Aug; 50(8): 677-82
ISSN: 0105-4538
PY: 1995
LA: ENGLISH
CP: DENMARK
AB: An optimal stimulation of CD4+ cells in an immune response requires not only signals transduced via the TcR/CD3 complex, but also costimulatory signals delivered as a consequence of interactions between T-cell surface-associated costimulatory receptors and their counterparts on antigen-presenting cells (APC). The intercellular adhesion molecule-1 (ICAM-1, CD54) efficiently costimulates proliferation of resting, but not antigen-specific, T cells. In contrast, CD28 and CD2 support interleukin (IL)-2 synthesis and proliferation of antigen-specific T cells more efficiently than those of resting T cells. The molecular basis for this differential costimulation of T cells is poorly understood. Cypress-specific T-cell clones (TCC) were generated from four allergic subjects during in vivo seasonal exposure to the allergen. Purified cypress extract was produced directly from fresh collected pollen and incubated with the patients' mononuclear cells. Repeated allergen stimulation was performed in T-cell cultures supplemented with purified extract and autologous APC. The limiting-dilution technique was then adopted to generate allergen-specific TCC, which were also characterized by their cytokine secretion pattern as Th0 (IL-4 plus interferon-gamma) or Th2 (IL-4). Costimulation-induced proliferation or apoptosis was measured by propidium iodide cytofluorometric assay. By cross-linking cypress-specific CD4+ and CD8+ T-cell clones with either anti-CD3 or anti-CD2, anti-CD28, and anti-CD54 monoclonal antibodies, we demonstrated that CD4+ clones (with Th0- or Th2-type cytokine production pattern) undergo programmed cell death only after anti-CD3 stimulation, whereas costimulation with either anti-CD54 or anti-CD28 protects target cells from apoptosis.(ABSTRACT TRUNCATED AT 250 WORDS)
MESH: Antigen-Presenting-Cells-immunology; Antigens,-CD2-immunology; Antigens,-CD28-immunology; Cell-Division; Cells,-Cultured; Clone-Cells; Hay-Fever-immunology; Intercellular-Adhesion-Molecule-1-immunology; Interleukin-1-metabolism; Pollen-immunology
MESH: *Allergens-immunology; *Antigens,-CD3-immunology; *Apoptosis-physiology; *CD4-Positive-T-Lymphocytes-immunology; *CD8-Positive-T-Lymphocytes-immunology; *Integrins-immunology; *Receptors,-Antigen,-T-Cell-immunology
TG: Human
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0; 126547-89-5
NM: Allergens; Antigens,-CD2; Antigens,-CD28; Antigens,-CD3; Integrins; Interleukin-1; Receptors,-Antigen,-T-Cell; Intercellular-Adhesion-Molecule-1
AN: 96098155
UD: 9603
MEDLINE EXPRESS (R) 1/96-12/96 20 of 125
TI: VLA-4/VCAM-1 pathway in human periodontal disease.
AU: Tsurumachi-T; Nishi-K; Hayashi-M; Saito-T; Saito-I; Moro-I
AD: Department of Endodontics, Nihon University School of Dentistry, Tokyo, Japan.
SO: Adv-Exp-Med-Biol. 1995; 371B: 1131-3
ISSN: 0065-2598
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
MESH: E-Selectin-genetics; Gene-Expression; Intercellular-Adhesion-Molecule-1-genetics; Interleukin-1-pharmacology; Kinetics-; Periapical-Periodontitis-genetics; Polymerase-Chain-Reaction; RNA,-Messenger-biosynthesis; RNA,-Messenger-genetics
MESH: *Integrins-genetics; *Periapical-Periodontitis-immunology; *Receptors,-Lymphocyte-Homing-genetics; *Vascular-Cell-Adhesion-Molecule-1-genetics
TG: Human
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0; 126547-89-5
NM: integrin-alpha4beta1; E-Selectin; Integrins; Interleukin-1; Receptors,-Lymphocyte-Homing; RNA,-Messenger; Vascular-Cell-Adhesion-Molecule-1; Intercellular-Adhesion-Molecule-1
AN: 96001706
UD: 9603
MEDLINE EXPRESS (R) 1/96-12/96 21 of 125
TI: Presence of T cells with activated and memory phenotypes in inflammatory spinal cord lesions.
AU: Barten-DM; Clark-RB; Ruddle-NH
AD: Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520, USA.
SO: J-Immunol. 1995 Dec 1; 155(11): 5409-18
ISSN: 0022-1767
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: The phenotypic and functional characteristics of activated T cells and recruited unactivated T cells at an inflammatory site were examined using a V beta 4+ myelin basic protein-specific T cell clone in a passively transferred model of experimental allergic encephalomyelitis. A high percentage of the T cells isolated from the central nervous system (CNS) were V beta 4+. This population exhibited the characteristics of activated T cells based on the proportion of cells in the blast state, their ability to proliferate in response to IL-2 or CNS Ag, and their expression of activation/memory cell markers. Activated V beta 4+ T cells were also observed in the periphery. Large numbers of V beta 4- T cells, which are entirely host-recruited, were also found in the CNS, where they demonstrated the properties of memory cells. There were differences in adhesion molecule expression between CNS V beta 4+ T cells and peripheral V beta 4+ T cells, although both populations were in activated state. V beta 4+ T cells at the site of Ag expression (the spinal cord) demonstrated higher levels of LFA-1 and CD44, but lower levels of VLA-4 and intercellular adhesion molecule-1, than did V beta 4+ T cells in the spleen. In contrast, the levels of all of these adhesion molecules on recruited V beta 4- T cells were higher in the CNS than in the periphery. This experimental model allows the detailed characterization of different T cell populations isolated from the same inflammatory site.
MESH: Antigens,-CD44-biosynthesis; Cells,-Cultured; Encephalomyelitis,-Allergic-etiology; Encephalomyelitis,-Allergic-pathology; Immunization,-Passive; Integrins-biosynthesis; Intercellular-Adhesion-Molecule-1-biosynthesis; Interleukin-2-immunology; Lymphocyte-Function-Associated-Antigen-1-biosynthesis; Lymphocyte-Transformation-immunology; Mice-; Mice,-Inbred-Strains; Myelin-Basic-Proteins-immunology; Receptors,-Antigen,-T-Cell,-alpha-beta-biosynthesis; Receptors,-Antigen,-T-Cell,-alpha-beta-immunology; Receptors,-Interleukin-2-biosynthesis; Receptors,-Lymphocyte-Homing-biosynthesis; Spinal-Cord-immunology; Spleen-cytology
MESH: *Encephalomyelitis,-Allergic-immunology; *Immunologic-Memory-immunology; *Lymphocyte-Transformation; *Spinal-Cord-pathology; *T-Lymphocytes-immunology
TG: Animal; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: 1F32NS09078NSNINDS
RN: 0; 0; 0; 0; 0; 0; 0; 0; 0; 126547-89-5
NM: integrin-alpha4beta1; Antigens,-CD44; Integrins; Interleukin-2; Lymphocyte-Function-Associated-Antigen-1; Myelin-Basic-Proteins; Receptors,-Antigen,-T-Cell,-alpha-beta; Receptors,-Interleukin-2; Receptors,-Lymphocyte-Homing; Intercellular-Adhesion-Molecule-1
AN: 96072821
UD: 9602
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 22 of 125
TI: Signal transduction through chondrocyte integrin receptors induces matrix metalloproteinase synthesis and synergizes with interleukin-1.
AU: Arner-EC; Tortorella-MD
AD: Du Pont Merck Pharmaceutical Company, Wilmington, DE 19880-0400, USA.
SO: Arthritis-Rheum. 1995 Sep; 38(9): 1304-14
ISSN: 0004-3591
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: OBJECTIVE. To study the role of signal transduction via integrin receptors in the production of metalloproteinase by rabbit articular chondrocytes. METHODS. Confluent, primary rabbit articular chondrocytes (RAC) were incubated for 72 hours in the presence of interleukin-1 (IL-1), Arg-Gly-Asp (RGD) peptide, or a combination of IL-1 and RGD peptide. Media were analyzed for stromelysin enzymatic activity using a 3H-labeled transferrin substrate, and for stromelysin and collagenase protein by Western analysis. Gelatinase activity was analyzed by gelatin zymography. IL-1 receptor antagonist (IL-1Ra) protein was used to determine the involvement of IL-1 in mediating the effects of RGD peptide, and fluorescence-activated cell sorter analysis (FACS) was used to examine the effect of IL-1 on chondrocyte integrin subunit expression. RESULTS. RGD peptides induced chondrocyte synthesis of stromelysin, collagenase, and 92-kd gelatinase B, and increased synthesis of the constitutively expressed 72-kd gelatinase A. Further studies focusing on stromelysin demonstrated that this up-regulation was concentration dependent and that RGD peptides synergized with IL-1 in inducing stromelysin synthesis. RGD-induced stromelysin production was inhibited by the IL-1Ra in a concentration-dependent manner, indicating that induction by RGD requires binding of IL-1 to its receptor. FACS analysis of RAC showed that IL-1 stimulation increased the expression of beta 1 and alpha v integrin subunits on the chondrocyte surface. CONCLUSION. Our data demonstrate that signal transduction through chondrocyte integrin receptors up-regulates metalloproteinase expression and that this is likely mediated through induction of IL-1. They also suggest that the binding of adhesion molecules to their chondrocyte integrin receptors reduces the amount of IL-1 required to induce stromelysin synthesis. Up-regulation of chondrocyte integrin expression by IL-1 may play a role in the synergistic effects seen with a combination of IL-1 and RGD peptides. Since elevated levels of both IL-1 and adhesion molecules are present in rheumatoid arthritis and osteoarthritis synovial fluid, our data suggest that this interaction may be important in mediating the cartilage destruction accompanying these diseases.
MESH: Cartilage-cytology; Cells,-Cultured; Drug-Synergism; Enzyme-Induction; Fibronectins-pharmacology; Interleukin-1-pharmacology; Oligopeptides-pharmacology; Peptide-Fragments-pharmacology; Rabbits-; Receptors,-Interleukin-1-antagonists-and-inhibitors
MESH: *Cartilage-metabolism; *Extracellular-Matrix-metabolism; *Integrins-physiology; *Interleukin-1-metabolism; *Metalloproteinases-metabolism; *Signal-Transduction
TG: Animal; Male
PT: JOURNAL-ARTICLE
RN: EC 3.4.24; 0; 0; 0; 0; 0; 0; 99896-85-2
NM: Metalloproteinases; Fibronectins; Integrins; Interleukin-1; Oligopeptides; Peptide-Fragments; Receptors,-Interleukin-1; arginyl-glycyl-aspartic-acid
AN: 96016062
UD: 9601
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 23 of 125
TI: Effect of interleukin-5 and granulocyte-macrophage colony stimulating factor on in vitro eosinophil function: comparison with airway eosinophils.
AU: Sedgwick-JB; Quan-SF; Calhoun-WJ; Busse-WW
AD: Department of Medicine, University of Wisconsin, Madison, USA.
SO: J-Allergy-Clin-Immunol. 1995 Sep; 96(3): 375-85
ISSN: 0091-6749
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: Eosinophils are hypothesized to be crucial in the development of allergic airway inflammation; however, the actual mechanisms that determine their inflammatory activity are still largely undefined. To investigate the factors that regulate eosinophil function in allergic airway disease, we have previously used segmental bronchoprovocation with allergen to study ex vivo eosinophil function. To determine whether the functional changes associated with airway eosinophils obtained by bronchoalveolar lavage 48 hours after antigen challenge are caused by exposure to airway-generated cytokines, normodense blood eosinophils were cultured in vitro with recombinant human interleukin-5 (IL-5) or granulocyte-macrophage colony stimulating factor (GM-CSF). The effect of cytokine exposure was then evaluated on selected cell functions. In vitro incubation with these cytokines for 24 hours significantly increased eosinophil membrane expression of CD18 and CD11b compared with culture in medium alone or eosinophils obtained by bronchoalveolar lavage. N-formyl-methionyl-leucyl-phenylalanine-stimulated superoxide anion generation was slightly but significantly enhanced by incubation with IL-5 but not with GM-CSF. In addition, spontaneous adhesion to human umbilical vein endothelial cell monolayers was increased after exposure to both IL-5 and GM-CSF. However, activated adhesion was enhanced only by culture with IL-5 and stimulation with N-formyl-methionyl-leucyl-phenylalanine. The magnitude of functional changes after in vitro preincubation of eosinophils with these cytokines did not achieve levels of superoxide anion and adhesion noted with airway eosinophils obtained after segmental bronchoprovocation with allergen. These observations raise the possibility that the contribution of IL-5 and GM-CSF to phenotypic changes of airway eosinophils is principally to enhance survival and expression of adhesion proteins. These data also suggest that, in addition to the generation of proinflammatory cytokines, other factors contribute to phenotypic changes in eosinophils as they migrate from the blood to the airway.
MESH: Blood-Cells-drug-effects; Blood-Cells-physiology; Bronchoalveolar-Lavage-Fluid-cytology; Cell-Adhesion-drug-effects; Cell-Survival-drug-effects; Cells,-Cultured; Cytokines-pharmacology; Eosinophils-physiology; Hay-Fever-pathology; Integrins-metabolism; Rhinitis,-Allergic,-Perennial-pathology; Superoxides-metabolism
MESH: *Eosinophils-drug-effects; *Granulocyte-Macrophage-Colony-Stimulating-Factor-pharmacology; *Interleukin-5-pharmacology
TG: Comparative-Study; Human; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: RO1AI23181AINIAID; RO1HL44098HLNHLBI
RN: 0; 0; 0; 11062-77-4; 83869-56-1
NM: Cytokines; Integrins; Interleukin-5; Superoxides; Granulocyte-Macrophage-Colony-Stimulating-Factor
AN: 96013053
UD: 9601
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 24 of 125
TI: T-lymphocyte responsiveness in murine schistosomiasis mansoni is dependent upon the adhesion molecules intercellular adhesion molecule-1, lymphocyte function-associated antigen-1, and very late antigen-4.
AU: Langley-JG; Boros-DL
AD: Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
SO: Infect-Immun. 1995 Oct; 63(10): 3980-6
ISSN: 0019-9567
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: Granuloma formation in murine schistosomiasis is dependent on CD4+ Th lymphocytes and requires recruitment and accumulation of inflammatory cells at the site of egg deposition. The present study examined the role of three adhesion molecules, intercellular adhesion molecule-1 (ICAM-1), lymphocyte function-associated antigen-1 (LFA-1), and very late antigen-4 (VLA-4), that participate in cellular recruitment, interaction, and lymphocyte activation during in vitro activation of acutely and chronically infected spleen and liver granuloma lymphocytes. Blockade of ICAM-1, LFA-1, or VLA-4 by rat monoclonal antibody inhibited spleen and granuloma lymphocyte interleukin-2 (IL-2) and IL-4 production as well as lymphoproliferative responses at similar levels (66 to 87%). The down-modulated cytokine and proliferative responses of chronically infected lymphocytes were inhibited to the same extent as their acutely infected counterparts. Cell sorting analysis demonstrated that acutely and chronically infected splenic and granuloma lymphocytes expressed similar levels of LFA-1, ICAM-1, and VLA-4 and that more ICAM-1 was expressed on infected than on uninfected mouse lymphocytes. By exposure of cells to paired monoclonal antibodies at suboptimal doses, it was determined that whereas all three adhesion molecules may participate, only ICAM-1 and LFA-1 showed synergistic interactions in determining lymphocyte responsiveness. These data suggest that spleen and liver granuloma lymphocytes are equally well armed with functional adhesion receptors. Thus, ICAM-1, LFA-1, and VLA-4 play an important accessory role in inflammatory cytokine production and lymphocyte proliferation, and therefore these adhesion molecules may participate in the initiation and maintenance of the granulomatous inflammation.
MESH: Antibodies,-Monoclonal-immunology; Cytokines-biosynthesis; Granuloma-etiology; Integrins-analysis; Intercellular-Adhesion-Molecule-1-analysis; Lymphocyte-Function-Associated-Antigen-1-analysis; Mice-; Mice,-Inbred-CBA; Rats-; Receptors,-Lymphocyte-Homing-analysis
MESH: *Integrins-physiology; *Intercellular-Adhesion-Molecule-1-physiology; *Lymphocyte-Function-Associated-Antigen-1-physiology; *Receptors,-Lymphocyte-Homing-physiology; *Schistosomiasis-mansoni-immunology; *T-Lymphocytes-immunology
TG: Animal; Female; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: AI12913AINIAID
RN: 0; 0; 0; 0; 0; 0; 126547-89-5
NM: integrin-alpha4beta1; Antibodies,-Monoclonal; Cytokines; Integrins; Lymphocyte-Function-Associated-Antigen-1; Receptors,-Lymphocyte-Homing; Intercellular-Adhesion-Molecule-1
AN: 96009755
UD: 9601
MEDLINE EXPRESS (R) 1991-1995 25 of 125
TI: Functional characteristics of mature granulocytes in a patient with acute promyelocytic leukemia treated with all-trans retinoic acid.
AU: Sham-RL; Phatak-PD; Belanger-KA; Braggins-C; Packman-CH
AD: Department of Medicine, Rochester General Hospital, NY 14621, USA.
SO: Leuk-Res. 1995 Aug; 19(8): 505-11
ISSN: 0145-2126
PY: 1995
LA: ENGLISH
CP: ENGLAND
AB: All-trans retinoic acid (ATRA) is a differentiating agent that has been successfully used in the treatment of patients with acute promyelocytic leukemia (APL). Functional properties of peripheral blood neutrophils from a patient with APL during treatment with ATRA have been studied. Wright stain of patient neutrophils showed hypogranulation and loose nuclear chromatin when compared with normal neutrophils. These cells were of lower density than normal neutrophils and separated on density gradient centrifugation with mononuclear cells. Surface antigen expression by FACS distinguished these cells from lymphocytes. The histograms showed a population of larger cells expressing CD18 and CD11b, distinct from the smaller cells which did not express CD11b. fMLP caused an increase in intracellular calcium (measured spectrophotometrically) that was inhibited by the calcium chelator BAPTA. Actin polymerization following cell activation was measured using NBD-phallacidin staining and FACS. Both IL-8 and fMLP caused rapid increases using F-actin content (2.5-3.0 fold), which were of greater magnitude than generally seen with normal neutrophils. Treatment with BAPTA before activation with fMLP did not blunt the actin responses, despite complete inhibition of an intracellular calcium increase. In summary, neutrophils derives from differentiated APL cells express CD18/CD11b, and exhibit a similar degree of actin polymerization in response to fMLP and IL-8, independent of an increase in intracellular calcium. Although the actin responses are greater than normal neutrophils, most properties are similar, supporting the contention that these cells can protect the host. The exaggerated actin response to inflammatory mediators, however, may play a role in the 'retinoic acid syndrome'.
MESH: Actins-metabolism; Antigens,-Surface-metabolism; Calcium-metabolism; Cell-Adhesion-Molecules-metabolism; Cell-Size-drug-effects; Granulocytes-drug-effects; Immunophenotyping-; Integrins-metabolism; Interleukin-8-pharmacology; Middle-Age; N-Formylmethionine-Leucyl-Phenylalanine-pharmacology
MESH: *Granulocytes-physiology; *Leukemia,-Promyelocytic,-Acute-drug-therapy; *Tretinoin-therapeutic-use
TG: Case-Report; Human; In-Vitro; Male; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 126880-86-2; 302-79-4; 59880-97-6; 7440-70-2
NM: Actins; Antigens,-Surface; Cell-Adhesion-Molecules; Integrins; Interleukin-8; L-Selectin; Tretinoin; N-Formylmethionine-Leucyl-Phenylalanine; Calcium
AN: 95387636
UD: 9512
MEDLINE EXPRESS (R) 1991-1995 26 of 125
TI: Modulation of the adhesion of hemopoietic progenitor cells to the RGD site of fibronectin by interleukin 3.
AU: Hardy-CL; Minguell-JJ
AD: Department of Veterans Affairs Medical Center, Jackson, Mississippi 39216, USA.
SO: J-Cell-Physiol. 1995 Aug; 164(2): 315-23
ISSN: 0021-9541
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: The integrins are a class of adhesion molecules which have been implicated in the homing of hemopoietic stem cells and in their restriction within the bone marrow. Integrins function as mediators of cell-extracellular matrix (ECM) interactions amd also of cell-cell interactions. They are unique membrane receptors which are capable of activation, change in affinity, and change in expression. Because of their broad potential for modulation we examined the effect of a cytokine growth factor which is present constitutively in the marrow, interleukin 3 (IL3), on integrin-mediated adherence of hemopoietic progenitor cells to the matrix component fibronectin (FN). The multipotential murine cell line B6Sut and the committed granulocyte progenitor cell line FDCP-1 were used. Both of these cell lines have been shown to bind to FN-coated dishes and to dishes coated with the 120 kDa and 40 kDa chymotryptic fragments of FN. It was found that after a brief withdrawal of IL3 the cells lost 80% adherence to the 120 kDa FN fragment containing the RGD cell binding site. This loss of binding was not related to a loss of viability, appeared unrelated to the growth/survival activity of IL3, and was quickly reversible by readdition of the growth factor. Adhesion of these cells to the RGD site was likely mediated by alpha 5 beta 1 integrin which was identified in the cell membrane of both cell lines, but present in low copy number in B6Sut cells. Two antibodies against the external and internal domains of alpha 5 and one antibody against beta 1 were used to study expression of the integrin. By flow cytometry the expression of alpha 5 was found to decrease in both cell lines by 4 h in the absence of IL3. The relative mean fluorescence intensity for B6Sut cells decreased from 1.0 (control cells always in the presence of IL3) to 0.6 over 4 h, and for FDCP-1 cells the decrement was from 1.0 to 0.8. The loss of RGD-mediated adhesion in the absence of IL3 appeared to proceed through this decrement in expression of the integrin; a loss of affinity of the receptor for its substrate was not detected. The general modulation of integrin activity by growth factors is of great interest because of its potential negative impact on the endothelium in cytokine-treated patients, and also because of its potential positive impact on engraftment during clinical bone marrow transplantation.
MESH: Cell-Adhesion-drug-effects; Cell-Line; Chymotrypsin-; Dose-Response-Relationship,-Drug; Hematopoietic-Stem-Cells-drug-effects; Integrins-metabolism; Kinetics-; Mice-; Oligopeptides-pharmacology; Peptide-Fragments-physiology; Receptors,-Fibronectin-metabolism
MESH: *Fibronectins-physiology; *Hematopoietic-Stem-Cells-physiology; *Interleukin-3-pharmacology; *Oligopeptides-physiology
TG: Animal; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-Non-P.H.S.
PT: JOURNAL-ARTICLE
RN: EC 3.4.21.1; 0; 0; 0; 0; 0; 0; 96426-21-0; 99896-85-2
NM: Chymotrypsin; Fibronectins; Integrins; Interleukin-3; Oligopeptides; Peptide-Fragments; Receptors,-Fibronectin; glycyl-arginyl-glycyl-aspartyl-serine; arginyl-glycyl-aspartic-acid
AN: 95348206
UD: 9511
MEDLINE EXPRESS (R) 1991-1995 27 of 125
TI: Expression and functional significance of an activation-dependent epitope of the beta 1 integrins in chronic inflammatory diseases.
AU: Arroyo-AG; Garcia-Vicuna-R; Marazuela-M; Yednock-TA; Gonzalez-Amaro-R; Sanchez-Madrid-F
AD: Servicio de Inmunologia, Hospital de la Princesa, Universidad Autonoma, Madrid, Spain.
SO: Eur-J-Immunol. 1995 Jun; 25(6): 1720-8
ISSN: 0014-2980
PY: 1995
LA: ENGLISH
CP: GERMANY
AB: The avidity of VLA integrins for their ligands can be increased by their transition to an active conformational state. This conformational change can be detected with a novel monoclonal antibody (mAb), termed 15/7, that recognizes an activation-dependent conformational epitope on the common beta 1 polypeptide of different VLA alpha beta 1 integrins. In an attempt to understand the possible role of the active conformational state of beta 1 integrins in vivo, we first investigated the expression of 15/7 epitope on T lymphocytes from patients with chronic inflammatory joint diseases. An enhanced expression of the 15/7 epitope was found in the synovial fluid (SF) T lymphocytes from these patients as compared to their peripheral blood (PB) T cells. The effect of different cytokines on the appearance of the 15/7 activation epitope in PB T lymphocytes was subsequently analyzed; interferon-gamma, interleukin-2 and, to a lower extent, tumor necrosis factor-alpha were able to induce an increased expression of the 15/7 epitope. This enhanced 15/7 expression correlated with a higher binding ability to fibronectin of cytokine-activated T cells. The presence of this activation epitope was detected in a small proportion of T lymphocytes scattered within inflammatory foci of synovial membrane from rheumatoid arthritis and thyroid glands from Hashimoto's chronic thyroiditis. We then analyzed the possible role of 15/7 epitope expression on cell adhesion in vitro. Immunofluorescence studies showed that the 15/7 epitope displayed a spot-like distribution, selectively decorating adhesive contacts of U-937 myelomonocytic cells attached to the 80 kDa proteolytic fragment of fibronectin (FN80). Furthermore, the anti-beta 1 15/7 mAb was able to induce both T lymphocyte, Jurkat and U-937 cellular binding and spreading on FN80. Altogether these results indicate that an activated conformation of beta 1 integrins is detected in vivo in lymphocyte infiltrates from chronic inflammatory conditions. The active conformations of beta 1 integrins are regulated by physiologic mediators such as cytokines, play an important role in cellular attachment and spreading, and appear to be involved in the development of inflammatory processes.
MESH: Arthritis,-Rheumatoid-pathology; Cytokines-metabolism; Cytokines-pharmacology; Epitopes-immunology; Immunohistochemistry-; Integrins-chemistry; Integrins-immunology; Organ-Specificity; T-Lymphocytes-metabolism
MESH: *Arthritis,-Rheumatoid-immunology; *Integrins-biosynthesis; *T-Lymphocytes-immunology
TG: Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0
NM: Antigens,-CD29; Cytokines; Epitopes; Integrins
AN: 95339889
UD: 9510
MEDLINE EXPRESS (R) 1991-1995 28 of 125
TI: Interaction of mast cells with extracellular matrix proteins.
AU: Metcalfe-DD
AD: Allergic Diseases Section, NIAID/NIH, Bethesda, MD 20892, USA.
SO: Int-Arch-Allergy-Immunol. 1995 May-Jun; 107(1-3): 60-2
ISSN: 1018-2438
PY: 1995
LA: ENGLISH
CP: SWITZERLAND
AB: It is possible to divide surface receptors on mast cells conceptually into three groups. The first consists of immune response receptors. The index receptor for this group is Fc epsilon RI, now joined by Fc gamma receptors and receptors for complement products. The second group of receptors are those that are involved in growth and differentiation, such as those for interleukin-3 and stem cell factor. The third group consists of receptors regulating mast cell trafficking and distribution. Principle among the latter group of receptors are those that engage extracellular matrix components, including the classical integrin receptors. The engagement of mast cells to matrix components not only has relevance in determining the tissue distribution of mast cells, but also appears to have a major influence on the biologic responsiveness of mast cells to immune- and growth-factor-receptor-mediated signals.
MESH: Amino-Acid-Sequence; Cell-Adhesion-drug-effects; Hematopoietic-Cell-Growth-Factors-pharmacology; Mast-Cells-drug-effects; Mice-; Molecular-Sequence-Data; Rats-; Receptors,-IgE-metabolism
MESH: *Extracellular-Matrix-Proteins-metabolism; *Integrins-metabolism; *Mast-Cells-metabolism
TG: Animal; Human
PT: JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL
RN: 0; 0; 0; 0; 0
NM: Extracellular-Matrix-Proteins; Hematopoietic-Cell-Growth-Factors; Integrins; Receptors,-IgE; Stem-Cell-Factor
AN: 95337849
UD: 9510
MEDLINE EXPRESS (R) 1991-1995 29 of 125
TI: Integrin-mediated tyrosine phosphorylation and cytokine message induction in monocytic cells. A possible signaling role for the Syk tyrosine kinase.
AU: Lin-TH; Rosales-C; Mondal-K; Bolen-JB; Haskill-S; Juliano-RL
AD: Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill 27599, USA.
SO: J-Biol-Chem. 1995 Jul 7; 270(27): 16189-97
ISSN: 0021-9258
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: Activation of cytoplasmic tyrosine kinases is an important aspect of signal transduction mediated by integrins. In the human monocytic cell line THP-1, either integrin-dependent cell adhesion to fibronectin or ligation of beta 1 integrins with antibodies causes a rapid and intense tyrosine phosphorylation of two sets of proteins of about 65-75 and 120-125 kDa. In addition, integrin ligation leads to nuclear translocation of the p50 and p65 subunits of the NF-kappa B transcription factor, to activation of a reporter gene driven by a promoter containing NF-kappa B sites, and to increased levels of mRNAs for immediate-early genes, including the cytokine interleukin (IL)-1 beta. The tyrosine kinase inhibitors genistein and herbimycin A block both integrin-mediated tyrosine phosphorylation and increases in IL-1 beta message levels, indicating a causal relationship between the two events. The components tyrosine phosphorylated subsequent to cell adhesion include paxillin, pp125FAK, and the SH2 domain containing tyrosine kinase Syk. In contrast, integrin ligation with antibodies induces tyrosine phosphorylation of Syk but not of FAK or paxillin. In adhering cells, pre-treatment with cytochalasin D suppresses tyrosine phosphorylation of FAK and paxillin but not of Syk, while IL-1 beta message induction is unaffected. These observations indicate that the Syk tyrosine kinase may be an important component of an integrin signaling pathway in monocytic cells, leading to activation of NF-kappa B and to increased levels of cytokine messages.
MESH: Cell-Adhesion-physiology; Cell-Adhesion-Molecules-metabolism; Enzyme-Activation; Enzyme-Precursors-antagonists-and-inhibitors; Extracellular-Matrix-Proteins-metabolism; Fibronectins-metabolism; Gene-Expression-Regulation,-Neoplastic; Genes,-Reporter; Inflammation-; Interleukin-1-genetics; Isoflavones-pharmacology; Leukemia,-Monocytic,-Acute; NF-kappa-B-metabolism; Phosphorylation-; Protein-Tyrosine-Kinase-antagonists-and-inhibitors; Quinones-pharmacology; RNA,-Messenger-biosynthesis; Tumor-Cells,-Cultured; Tyrosine-metabolism
MESH: *Enzyme-Precursors-metabolism; *Integrins-metabolism; *Interleukin-1-biosynthesis; *Monocytes-metabolism; *Protein-Tyrosine-Kinase-metabolism; *Signal-Transduction
TG: Comparative-Study; Human; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
RN: EC 2.7.1.-; EC 2.7.1.-; EC 2.7.1.112; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 446-72-0; 55520-40-6; 70563-58-5
NM: endogenous-substrate-pp120; p72syk; Protein-Tyrosine-Kinase; Antigens,-CD29; Cell-Adhesion-Molecules; Enzyme-Precursors; Extracellular-Matrix-Proteins; Fibronectins; Integrins; Interleukin-1; Isoflavones; NF-kappa-B; Quinones; RNA,-Messenger; genistein; Tyrosine; herbimycin
AN: 95332324
UD: 9510
MEDLINE EXPRESS (R) 1991-1995 30 of 125
TI: Up-regulation of integrin alpha 5 beta 1 expression by interleukin-6 in rabbit corneal epithelial cells.
AU: Ohashi-H; Maeda-T; Mishima-H; Otori-T; Nishida-T; Sekiguchi-K
AD: Research Institute, Osaka Medical Center for Maternal and Child Health, Japan.
SO: Exp-Cell-Res. 1995 Jun; 218(2): 418-23
ISSN: 0014-4827
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: Interleukin-6 (IL-6) has been shown to promote the attachment of rabbit corneal epithelial cells to fibronectin-coated substratum and ex vivo migration of the cells on the corneal stroma. To examine whether IL-6 promotes cell attachment through up-regulation of expression of integrin alpha 5 beta 1, i.e., the major cell surface fibronectin receptor, we quantified the levels of both alpha 5 and beta 1 subunit transcripts by reverse transcription-polymerase chain reaction in cultured rabbit corneal epithelial cells pretreated with various concentrations of IL-6. The levels of both alpha 5 and beta 1 mRNAs were dose-dependently elevated by IL-6, attaining 1.5- and 1.8-fold increases, respectively, at 10 ng/ml. The stimulatory effect of IL-6 was transient; the levels of both subunit mRNAs reached a maximum 1 h after the addition of IL-6 and returned to the basal levels after 6 h. The IL-6-induced up-regulation of integrin alpha 5 and beta 1 mRNAs was also confirmed by Northern blot analysis. These results indicate that the increased attachment of corneal epithelial cells to fibronectin and enhanced ex vivo migration on corneal stroma by IL-6 is, at least in part, due to the temporal up-regulation of integrin alpha 5 beta 1 expression in corneal epithelial cells.
MESH: Amino-Acid-Sequence; Base-Sequence; Cells,-Cultured; Cornea-cytology; Corneal-Stroma-cytology; DNA-Primers; Integrins-chemistry; Molecular-Sequence-Data; Polymerase-Chain-Reaction; Rabbits-; Up-Regulation-Physiology
MESH: *Cornea-metabolism; *Integrins-biosynthesis; *Interleukin-6-pharmacology
TG: Animal; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0
NM: DNA-Primers; Integrins; Interleukin-6; Receptors,-Fibronectin
AN: 95317375
UD: 9510
MEDLINE EXPRESS (R) 1991-1995 31 of 125
TI: Bryostatin 1 enhances lymphokine activated killer sensitivity and modulates the beta 1 integrin profile of cultured human tumor cells.
AU: Correale-P; Caraglia-M; Fabbrocini-A; Guarrasi-R; Pepe-S; Patella-V; Marone-G; Pinto-A; Bianco-AR; Tagliaferri-P
AD: Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinica, Universita Federico II, Napoli, Italy.
SO: Anticancer-Drugs. 1995 Apr; 6(2): 285-90
ISSN: 0959-4973
PY: 1995
LA: ENGLISH
CP: ENGLAND
AB: Bryostatin 1 interferes with protein kinase C (PKC) signaling which is involved in the activation of human and murine cytotoxic T lymphocytes, and in the growth and differentiation of tumor cells. Bryostatin 1 has immunomodulating and antitumor properties as demonstrated by preclinical and clinical studies. Here we report that bryostatin 1 increases the susceptibility to lymphokine activated killers and modifies the pattern of beta 1 integrin expression of human tumor cells. On the basis of these results the use of bryostatin 1 in combination with immunostimulating cytokines such as interleukin-2 in the treatment of human cancer is suggested.
MESH: Tumor-Cells,-Cultured
MESH: *Adjuvants,-Immunologic-pharmacology; *Antineoplastic-Agents-pharmacology; *Integrins-analysis; *Killer-Cells,-Lymphokine-Activated-drug-effects; *Lactones-pharmacology
TG: Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 83314-01-6
NM: Adjuvants,-Immunologic; Antigens,-CD29; Antineoplastic-Agents; Integrins; Lactones; bryostatin-1
AN: 95315599
UD: 9510
MEDLINE EXPRESS (R) 1991-1995 32 of 125
TI: Monocyte modulation of endothelial leukocyte adhesion molecules.
AU: Weill-D; Wautier-JL; Dosquet-C; Wautier-MP; Carreno-MP; Boval-B
AD: Laboratoire de Biologie Vasculaire et Cellulaire, Universite de Paris VII, France.
SO: J-Lab-Clin-Med. 1995 Jun; 125(6): 768-74
ISSN: 0022-2143
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: Leukocyte adhesion to endothelium is dependent on expression of specialized molecules. Several of these molecules are upregulated by cytokines such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha). We investigated the effect of medium conditioned by unstimulated (MCM) or stimulated monocytes and of recombinant cytokines on endothelial adhesion receptor expression. IL-1 beta, TNF-alpha, and MCM induced E-selectin similarly, whereas MCM induced VCAM-1 and ICAM-1 to a lesser extent than did TNF-alpha, and MCM induced VCAM-1 only weakly. The addition of pentoxifylline (10(-3) mol/L) to monocytes during MCM preparation blocked TNF-alpha production but not that of IL-1 beta or IL-6, and it reduced IL-1ra significantly (p < 0.05). When the MCM was devoid of TNF-alpha or when TNF-alpha was neutralized with a specific antibody, the action of MCM on E-selectin expression was significantly lower. Anti-IL-1 beta decreased the activity of MCM on endothelial E-selectin expression by about 50%. The effect of MCM on adhesion molecules was accompanied by an increase in monocyte adhesion. Inhibition of TNF-alpha production reduced monocytes adhesion slightly but significantly (18%, p < 0.05), whereas anti-IL-1 beta antibody decreased adhesion by 48% (p < 0.001). These results show that adherent monocytes released cytokines and antagonists that affect leukocyte adhesion receptors on endothelium differently from recombinant cytokines. E-selectin expression--and to a lesser extent ICAM expression--is modified, resulting in a modulation of leukocyte adhesion to endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)
MESH: Cells,-Cultured; Culture-Media,-Conditioned; Endothelium,-Vascular-drug-effects; Gene-Expression-drug-effects; Integrins-analysis; Intercellular-Adhesion-Molecule-1-biosynthesis; Interleukin-1-biosynthesis; Interleukin-1-pharmacology; Interleukin-6-biosynthesis; Kinetics-; Pentoxifylline-pharmacology; Recombinant-Proteins-pharmacology; Sialoglycoproteins-biosynthesis; Sialoglycoproteins-pharmacology; Tumor-Necrosis-Factor-biosynthesis; Tumor-Necrosis-Factor-pharmacology; Umbilical-Veins
MESH: *Cell-Adhesion; *Cell-Adhesion-Molecules-biosynthesis; *Cytokines-pharmacology; *Endothelium,-Vascular-physiology; *Integrins-biosynthesis; *Leukocytes-physiology; *Monocytes-physiology
TG: Human; In-Vitro; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 126547-89-5; 6493-05-6
NM: interleukin-1-receptor-antagonist-protein; Cell-Adhesion-Molecules; Culture-Media,-Conditioned; Cytokines; E-Selectin; Integrins; Interleukin-1; Interleukin-6; Recombinant-Proteins; Sialoglycoproteins; Tumor-Necrosis-Factor; Vascular-Cell-Adhesion-Molecule-1; Intercellular-Adhesion-Molecule-1; Pentoxifylline
AN: 95287132
UD: 9509
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 33 of 125
TI: T lymphocyte locomotion in a three-dimensional collagen matrix. Expression and function of cell adhesion molecules.
AU: Friedl-P; Noble-PB; Zanker-KS
AD: Institute of Immunology, University of Witten/Herdecke, Germany.
SO: J-Immunol. 1995 May 15; 154(10): 4973-85
ISSN: 0022-1767
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: T cell locomotion within the extracellular matrix may be mediated by cell adhesion molecules. We investigated the expression and function of beta 1- and beta 2-integrins and CD44 on human peripheral CD4+ and CD8+ lymphocytes locomoting in a 3-D type I collagen matrix. Paths of randomly selected T cells were digitized from time-lapse videorecordings and were quantitatively analyzed. After the blocking of CD49b with mAb Gi9, the locomotion of a defined locomotor subset (50% of spontaneously locomoting cells) was inhibited. Anti-CD49d mAb HP2/1 and an activating anti-CD44 mAb (J173), respectively, induced transient recruitment (< 1 h) of previously nonmotile cells (10 to 35%). In contrast to the J173-induced short-term locomotion, hyaluronan incorporated within the matrix promoted locomotion for > 2 h. No significant effects were present for anti-CD49f (GoH3) and -CD11a (25.3) mAbs. After the addition of IL-8 to the matrix, rapid induction of locomotion in 20 to 30% of the cells (control) was evident, which was virtually abolished by anti-alpha 2- and alpha 6-integrin, and -CD11a mAbs. Thus, the locomotion of nonactivated and IL-8-activated T cells may involve different sets of integrins. Using flow cytometry, the development of a CD49b+CD29highCD44lowL-selectinlow T cell phenotype independent of activation markers including CD25, CD27, CD28, VLA-4, and CD45RA- to CD45RO-transition was observed after 4 days in the matrix. The initial development of spontaneous locomotion in the collagen matrix, however, was not accompanied by alterations in CAM surface staining and, therefore, may involve functional CAM activation rather than involving an increase in surface expression.
MESH: Antibodies,-Monoclonal-immunology; Antigens,-CD-biosynthesis; Cell-Adhesion-Molecules-biosynthesis; Cells,-Cultured; Collagen-; Culture-Media; Integrins-physiology; Interleukin-8-physiology; Lymphocyte-Function-Associated-Antigen-1-physiology; Receptors,-Very-Late-Antigen-physiology
MESH: *Cell-Adhesion-Molecules-physiology; *Cell-Movement-immunology; *T-Lymphocytes-physiology
TG: Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0; 0; 126880-86-2; 9007-34-5
NM: Antibodies,-Monoclonal; Antigens,-CD; Cell-Adhesion-Molecules; Culture-Media; Integrins; Interleukin-8; Lymphocyte-Function-Associated-Antigen-1; Receptors,-Very-Late-Antigen; L-Selectin; Collagen
AN: 95248062
UD: 9508
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 34 of 125
TI: The adhesion molecules used by monocytes for migration across endothelium include CD11a/CD18, CD11b/CD18, and VLA-4 on monocytes and ICAM-1, VCAM-1, and other ligands on endothelium.
AU: Meerschaert-J; Furie-MB
AD: Program in Molecular and Cellular Biology, School of Medicine, State University of New York at Stony Brook 11794, USA.
SO: J-Immunol. 1995 Apr 15; 154(8): 4099-112
ISSN: 0022-1767
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: CD11/CD18 and VLA-4 integrins mediate interactions of monocytes with HUVEC cultured on human amniotic tissue. In the present study, the roles of individual CD11/CD18 integrins and endothelial adhesion molecules were examined using blocking mAbs and peptides. After 20 min of incubation, monocyte adhesion to and migration across unstimulated endothelium was dependent primarily on CD11a/CD18. When incubation was extended to 2 h to allow for completion of migration, either CD11a/CD18 or CD11b/CD18 could be used. Similarly, either CD11a/CD18 or CD11b/CD18 could be used by monocytes to bind to and traverse IL-1 beta-stimulated endothelium. Although both CD11a/CD18 and CD11b/CD18 are known to bind to ICAM-1, results of Ab-mixing experiments suggest that alternative ligands on HUVEC for CD11/CD18 integrins also may be used during transendothelial migration of monocytes. Our previous studies indicate that VLA-4 on monocytes interacts primarily with VCAM-1 on unstimulated endothelium. In contrast, migration of monocytes across IL-1 beta-stimulated endothelium was less dependent on VCAM-1. mAbs directed against binding sites for VLA-4 in domain 1 and domain 4 of VCAM-1 did not, by themselves, inhibit interactions of monocytes with stimulated HUVEC. VLA-4-dependent migration across IL-1 beta-stimulated endothelium was markedly inhibited only when mAbs to VCAM-1 were added in combination with peptides of fibronectin. Therefore, VLA-4 can interact with either VCAM-1 or alternative ligands on IL-1 beta-stimulated HUVEC-amnion cultures to mediate transendothelial migration of monocytes.
MESH: Amino-Acid-Sequence; Antigens,-CD11-physiology; Antigens,-CD18-physiology; Endothelium,-Vascular-drug-effects; Integrins-physiology; Intercellular-Adhesion-Molecule-1-physiology; Interleukin-1-pharmacology; Ligands-; Molecular-Sequence-Data; Peptides-chemistry; Receptors,-Very-Late-Antigen-physiology
MESH: *Cell-Adhesion-Molecules-physiology; *Cell-Movement; *Endothelium,-Vascular-cytology; *Monocytes-cytology
TG: Human; In-Vitro; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0; 0; 0; 126547-89-5
NM: Antigens,-CD11; Antigens,-CD18; Cell-Adhesion-Molecules; Integrins; Interleukin-1; Ligands; Peptides; Receptors,-Very-Late-Antigen; Vascular-Cell-Adhesion-Molecule-1; Intercellular-Adhesion-Molecule-1
AN: 95221918
UD: 9507
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 35 of 125
TI: Cell-mediated immune status of children with recurrent infection.
AU: Herrod-HG; Blaiss-MS; Valenski-WR; Gross-S
AD: Crippled Children's Foundation Research Center, Le Bonheur Children's Medical Center, University of Tennessee, Memphis 38163, USA.
SO: J-Pediatr. 1995 Apr; 126(4): 530-6
ISSN: 0022-3476
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: OBJECTIVE: To evaluate the cell-mediated immune status of children with recurrent respiratory tract infections. DESIGN: We evaluated the cell-mediated immune status of 76 patients referred because of recurrent infection. Patients were divided into those with serologic abnormalities and those without such findings. Twenty-three healthy children served as control subjects. Studies of lymphocyte phenotype included CD4+ CD29+ cells (an immunologically mature phenotype), lymphocyte proliferation studies, cytokine production including interleukin-2 (IL-2), IL-4, IL-6, and interferon gamma), and measurement of in vitro IgM and IgG synthesis. RESULTS: Lymphocyte proliferation and T-cell phenotype were similar in both patient groups as well as in control subjects. The proportions of CD4+ CD29+ cells at different ages were similar in all groups. Patients with serologic abnormalities (e.g., partial IgA deficiency, partial IgG subclass deficiency) produced more IL-2 and IL-4 than did other patients. The control population had greater spontaneous IgM and IgG synthesis than the patient groups. CONCLUSION: Routine studies of T-cell function of patients with recurrent infection provide little information useful in making clinical decisions.
MESH: Antigens,-Bacterial-biosynthesis; Bacterial-Vaccines-immunology; Child-; Child,-Preschool; IgG-blood; IgM-blood; Immunity,-Cellular-immunology; Immunophenotyping-; Infant-; Interferon-Type-II-blood; Interleukin-2-blood; Interleukin-4-blood; Interleukin-6-blood; Lymphocyte-Transformation; Matched-Pair-Analysis; Recurrence-
MESH: *Antigens,-CD-analysis; *Antigens,-CD4-analysis; *Cytokines-blood; *Immunity,-Cellular; *Integrins-analysis; *Respiratory-Tract-Infections-immunology
TG: Human
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 82115-62-6
NM: pneumovax; Antigens,-Bacterial; Antigens,-CD; Antigens,-CD29; Antigens,-CD4; Bacterial-Vaccines; Cytokines; IgG; IgM; Integrins; Interleukin-2; Interleukin-4; Interleukin-6; Interferon-Type-II
AN: 95213885
UD: 9507
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 36 of 125
TI: Interleukin-4 induces expression of the integrin alpha v beta 3 via transactivation of the beta 3 gene.
AU: Kitazawa-S; Ross-FP; McHugh-K; Teitelbaum-SL
AD: Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.
SO: J-Biol-Chem. 1995 Feb 24; 270(8): 4115-20
ISSN: 0021-9258
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: Osteoclastic bone resorption is dependent upon cell-matrix recognition. This process is mediated by the integrin alpha v beta 3 whose expression is enhanced, in avian osteoclast precursors, by bone-seeking steroids. The purpose of this study was to determine if bone-modulating cytokines impact on alpha v beta 3 expression by mouse marrow macrophages (BMMs), known to differentiate into osteoclasts. Of the cytokines tested. Interleukin-4 (IL-4) is most effective in increasing beta 3 mRNA levels by a mechanism involving transactivation of the beta 3 gene. Moreover, IL-4 augmented beta 3 mRNA is mirrored by plasma membrane appearance of alpha v beta 3. As IL-4 induces beta 3 and not alpha v mRNA, the beta 3 chain appears to regulate surface expression of the heterodimer. The functional significance of IL-4-induced alpha v beta 3 is underscored by the fact that, while attachment to fibronectin is unaltered, treatment of BMMs with the cytokine enhances alpha v beta 3-mediated binding to vitronectin 5-fold. Expression of this heterodimer by BMMs driven along a non-osteoclastic lineage suggests alpha v beta 3 may play a role in the inflammatory response of macrophages.
MESH: Cells,-Cultured; Cytokines-physiology; Glycoproteins-metabolism; Integrins-metabolism; Mice-; Protein-Binding; Receptors,-Cytoadhesin-metabolism; RNA,-Messenger-genetics; RNA,-Messenger-metabolism
MESH: *Gene-Expression-Regulation; *Integrins-genetics; *Interleukin-4-physiology; *Receptors,-Cytoadhesin-genetics; *Trans-Activation-Genetics
TG: Animal; Male; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
GS: bgr3
PT: JOURNAL-ARTICLE
CN: DE05413DENIDR; AR42404ARNIAMS
RN: 0; 0; 0; 0; 0; 0; 0; 0
NM: Cytokines; Glycoproteins; Integrins; Interleukin-4; Receptors,-Cytoadhesin; Receptors,-Vitronectin; RNA,-Messenger; Vitronectin
AN: 95181382
UD: 9506
MEDLINE EXPRESS (R) 1991-1995 37 of 125
TI: Cytokines modulate in vitro invasiveness of renal cell carcinoma cells through action on the process of cell attachment to endothelial cells.
AU: Yanase-M; Tsukamoto-T; Kumamoto-Y
AD: Department of Urology, School of Medicine, Sapporo Medical University, Japan.
SO: J-Urol. 1995 Mar; 153(3 Pt 1): 844-8
ISSN: 0022-5347
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: Cytokines play important roles in adhesion between various cells and endothelium. Cell-cell adhesion is also a critical step in the invasion of interstitial tissue by cancer cells. Using an in vitro invasion assay modified by cultured human umbilical venule endothelial cells (HUVEC) and an extracellular matrix (Matrigel) membrane system, we studied how cytokines affect the invasiveness of human renal cell carcinoma cells through action on the endothelium. When HUVEC were treated for 6 hours with tumor necrosis factor (TNF, 100 or 1000 U/ml.), interleukin-1 (IL-1, 10 ng./ml.) or IL-6 (1.0 or 10 ng./ml.), the treatment significantly increased in vitro invasiveness of the carcinoma cells. Enhancement of carcinoma cell invasiveness reflected the enhancement by the cytokine treatments of the ability of HUVEC to express vascular cell adhesion molecule-1 (VCAM-1). Application of anti-VCAM-1 monoclonal antibody (mAb) suppressed in vitro invasion of the carcinoma cells when HUVEC were treated with the cytokines at the above concentrations. Moreover, an adherence assay demonstrated that a larger number of carcinoma cells adhered to the endothelium treated by the cytokines than to endothelium not receiving such treatment and that anti-VCAM-1 mAb application inhibited the adhesion. The cytokine treatment of HUVEC did not affect type IV collagenolysis. These results indicated that cytokines can enhance the in vitro invasiveness of carcinoma cells through their action on endothelium (that is, augmentation of VCAM-1 expression) in the in vitro invasion assay modified with HUVEC-Matrigel-reconstituted membrane.
MESH: Antibodies,-Monoclonal; Carcinoma,-Renal-Cell-metabolism; Cell-Adhesion; Cell-Adhesion-Molecules-biosynthesis; Cell-Adhesion-Molecules-immunology; Collagen-metabolism; Endothelium-cytology; Integrins-biosynthesis; Kidney-Neoplasms-metabolism; Neoplasm-Invasiveness; Tumor-Cells,-Cultured
MESH: *Carcinoma,-Renal-Cell-pathology; *Cytokines-physiology; *Kidney-Neoplasms-pathology
TG: Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 9007-34-5
NM: Antibodies,-Monoclonal; Cell-Adhesion-Molecules; Cytokines; Integrins; Vascular-Cell-Adhesion-Molecule-1; Collagen
AN: 95165568
UD: 9505
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 38 of 125
TI: Suppression of ICE and apoptosis in mammary epithelial cells by extracellular matrix.
AU: Boudreau-N; Sympson-CJ; Werb-Z; Bissell-MJ
AD: Life Sciences Division, Lawrence Berkeley Laboratory, Berkeley, CA 94720.
SO: Science. 1995 Feb 10; 267(5199): 891-3
ISSN: 0036-8075
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: Apoptosis (programmed cell death) plays a major role in development and tissue regeneration. Basement membrane extracellular matrix (ECM), but not fibronectin or collagen, was shown to suppress apoptosis of mammary epithelial cells in tissue culture and in vivo. Apoptosis was induced by antibodies to beta 1 integrins or by overexpression of stromelysin-1, which degrades ECM. Expression of interleukin-1 beta converting enzyme (ICE) correlated with the loss of ECM, and inhibitors of ICE activity prevented apoptosis. These results suggest that ECM regulates apoptosis in mammary epithelial cells through an integrin-dependent negative regulation of ICE expression.
MESH: Basement-Membrane; Cell-Line; Collagen-; Cysteine-Proteinase-Inhibitors-pharmacology; Cysteine-Proteinases-genetics; Extracellular-Matrix-metabolism; Fibronectins-; Gene-Expression-Regulation,-Enzymologic; Integrins-immunology; Mammae-enzymology; Metalloproteinases-genetics; Metalloproteinases-metabolism; Mice-; Mice,-Transgenic; RNA,-Messenger-genetics; RNA,-Messenger-metabolism; Transfection-
MESH: *Apoptosis-; *Cysteine-Proteinases-metabolism; *Extracellular-Matrix-physiology; *Mammae-cytology
TG: Animal; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-Non-P.H.S.; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: CA57621CANCI; ES07106ESNIEHS
RN: EC 3.4.22; EC 3.4.22.36; EC 3.4.24; EC 3.4.24.17; 0; 0; 0; 0; 0; 9007-34-5
NM: Cysteine-Proteinases; interleukin-1beta-converting-enzyme; Metalloproteinases; stromelysin-1; Antigens,-CD29; Cysteine-Proteinase-Inhibitors; Fibronectins; Integrins; RNA,-Messenger; Collagen
AN: 95149130
UD: 9505
MEDLINE EXPRESS (R) 1991-1995 39 of 125
TI: Comitogenic effects of very late activation antigens on CD3-stimulated human thymocytes. Involvement of various tyrosine kinase pathways.
AU: Ticchioni-M; Deckert-M; Bernard-G; Calandra-D; Breittmeyer-JP; Imbert-V; Peyron-JF; Bernard-A
AD: National Institute of Health and Medical Research (INSERM) Unit 343, Faculty of Medicine, Nice, France.
SO: J-Immunol. 1995 Feb 1; 154(3): 1207-15
ISSN: 0022-1767
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: Thymocytes display several integrins that are involved in cell-extracellular matrix interactions and differentiation processes. We have examined the role of very late activation Ag (VLA) on human thymocyte stimulation. VLA-4, VLA-5, and VLA-6 activated with either mAbs or their natural ligands (fibronectin, laminin, and vascular cell adhesion molecule-1) are able to transduce costimulatory signals in thymocytes activated via the CD3 pathway, i.e., enhancement of thymocyte proliferation, CD25 and CD69 expression, and IL-2 secretion. In contrast, activation of thymocytes with a mitogenic pair of CD2 mAb was not modified by VLA molecules. Cross-linking of both beta 1- and alpha 5-chains induced tyrosine phosphorylation of several proteins, whereas the cross-linking of the alpha 4- and alpha 6-chains did not. Moreover, a different pattern of tyrosine phosphorylation was observed when thymocytes were activated via either beta 1- or alpha 5-chains. These results suggest that VLA molecules activate tyrosine kinase pathways in thymocytes, and that different pathways would be implicated during thymocyte interactions with extracellular matrix or accessory cells, which are likely to play a role in thymocyte differentiation.
MESH: Antibodies,-Monoclonal-immunology; Antigens,-CD-immunology; Antigens,-CD2-immunology; Cells,-Cultured; Child,-Preschool; Immunoblotting-; Integrins-immunology; Interleukin-2-immunology; Signal-Transduction-immunology; Thymus-Gland-cytology
MESH: *Antigens,-CD3-immunology; *Lymphocyte-Transformation-immunology; *Protein-Tyrosine-Kinase-immunology; *Receptors,-Very-Late-Antigen-immunology; *T-Lymphocytes-immunology
TG: Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: EC 2.7.1.112; 0; 0; 0; 0; 0; 0; 0; 0
NM: Protein-Tyrosine-Kinase; Antibodies,-Monoclonal; Antigens,-CD; Antigens,-CD2; Antigens,-CD29; Antigens,-CD3; Integrins; Interleukin-2; Receptors,-Very-Late-Antigen
AN: 95123071
UD: 9504
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 40 of 125
TI: Expression of vitronectin receptor on human NK cells and its role in protein phosphorylation, cytokine production, and cell proliferation.
AU: Rabinowich-H; Lin-WC; Amoscato-A; Herberman-RB; Whiteside-TL
AD: Department of Pathology, University of Pittsburgh School of Medicine, PA 15213.
SO: J-Immunol. 1995 Feb 1; 154(3): 1124-35
ISSN: 0022-1767
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: In this paper, we provide evidence that the vitronectin receptor (VNR) alpha v beta 3 is expressed on human NK cells. The presence of this VNR on freshly purified NK cells was demonstrated by flow cytometry analysis, as well as biochemically, after 125I-labeled surface lactoperoxidase labeling and immunoprecipitation. mAbs LM142 and LM609 specific for alpha v and alpha v beta 3, respectively, precipitated a heterodimer of alpha- and beta-chains with approximate molecular masses of 155 and 110 kDa under nonreducing conditions. Under reducing conditions, there was an apparent decrease in the molecular mass of the alpha-chain, which is likely to result from the release of a protein of 20 to 30 kDa linked by internal disulfide bond to the alpha v-chain. Integrin alpha v beta 3 expressed on NK cells became functional, i.e., was able to bind its ligand, vitronectin (VN), only after cellular activation or when costimulation with an additional signal was provided. Thus, NK cells adhered to plastic-immobilized VN only after IL-2 activation, and RGD-containing synthetic peptides or mAbs specific for alpha v beta 3 complex inhibited this binding. To assess the role of the VNR in signal transduction, anti-beta 3 mAb was used to cluster the VNR on NK cells and, thereby, mimic the process that occurs during formation of adhesive contacts. Cross-linking of VNR on fresh NK cells stimulated phosphorylation on tyrosine residues of several intracellular proteins. The major increase in tyrosine phosphorylation was observed in proteins of approximate molecular masses of 75 and 120 kDa. Therefore, signal transduction by the VNR on NK cells induced activation of intracellular protein kinases. Ligand engagement of the VNR on NK cells also costimulated cytokine production and proliferation of NK cells. Binding of NK cells to plastic-immobilized VN served as a costimulus with either anti-Fc gamma RIII or IL-2 to produce IFN-gamma, TNF-alpha, and cell proliferation. Our findings suggest that occupancy and subsequent clustering of VNRs play a role in the activation and function of human NK cells.
MESH: Amino-Acid-Sequence; Antibodies,-Monoclonal-immunology; Blotting,-Western; Cell-Adhesion-immunology; Flow-Cytometry; Integrins-biosynthesis; Interleukin-2-physiology; Molecular-Sequence-Data; Precipitin-Tests; Receptors,-Cytoadhesin-biosynthesis; Signal-Transduction-immunology; Up-Regulation-Physiology-immunology
MESH: *Cytokines-biosynthesis; *Integrins-immunology; *Killer-Cells,-Natural-immunology; *Lymphocyte-Transformation-immunology; *Protein-Tyrosine-Kinase-metabolism; *Receptors,-Cytoadhesin-immunology
TG: Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: EC 2.7.1.112; 0; 0; 0; 0; 0; 0
NM: Protein-Tyrosine-Kinase; Antibodies,-Monoclonal; Cytokines; Integrins; Interleukin-2; Receptors,-Cytoadhesin; Receptors,-Vitronectin
AN: 95123063
UD: 9504
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 41 of 125
TI: IL-13 selectively induces vascular cell adhesion molecule-1 expression in human endothelial cells.
AU: Bochner-BS; Klunk-DA; Sterbinsky-SA; Coffman-RL; Schleimer-RP
AD: Department of Medicine, Johns Hopkins University School of Medicine, Johns Hopkins Asthma and Allergy Center, Baltimore, MD 21224.
SO: J-Immunol. 1995 Jan 15; 154(2): 799-803
ISSN: 0022-1767
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: Previous studies with human umbilical vein endothelial cells (HUVEC) have shown that the cytokine IL-4 induces adherence of human eosinophils, but not neutrophils, because of its ability to selectively induce surface expression of vascular cell adhesion molecule-1 (VCAM-1). Because the cytokine IL-13 shares a number of biologic properties with IL-4, we examined the effect of IL-13 on the expression and function of adhesion molecules on HUVEC. Incubation of HUVEC for 4 to 48 h with IL-13 (0.1 to 15 U/ml) induced surface expression of VCAM-1, as detected by indirect immunofluorescence and flow cytometry, without significantly affecting expression of E-selectin or intercellular adhesion molecule-1. The kinetics and maximal IL-13-induced expression of VCAM-1 were similar to those seen with IL-4. Treatment of HUVEC with an optimal concentration of IL-13 (15 U/ml for 24 h) induced adhesiveness for eosinophils, but not for neutrophils, and adhesion was completely inhibited by mAb recognizing VCAM-1 or alpha 4 integrin (CD49d). These results demonstrate that IL-13, like IL-4, selectively stimulates HUVEC to express functional cell surface VCAM-1 and suggest a possible role for IL-13 in promoting VCAM-1/alpha 4 integrin-dependent accumulation of eosinophils during allergic and other inflammatory reactions in vivo.
MESH: Cell-Adhesion-Molecules-biosynthesis; Cells,-Cultured; Eosinophils-physiology; Integrins-biosynthesis; Integrins-physiology; Neutrophils-physiology; Umbilical-Veins-cytology
MESH: *Cell-Adhesion-physiology; *Cell-Adhesion-Molecules-physiology; *Endothelium,-Vascular-metabolism; *Interleukin-13-physiology
TG: Human; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: AI27429AINIAID; HL49545HLNHLBI; AR31891ARNIAMS
RN: 0; 0; 0; 0; 143198-26-9
NM: Cell-Adhesion-Molecules; Integrins; Interleukin-13; Vascular-Cell-Adhesion-Molecule-1; alpha4-integrin
AN: 95114406
UD: 9504
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 42 of 125
TI: High expression of adhesion molecules/activation markers with little interleukin-2, interferon gamma, and tumor necrosis factor beta gene activation in fresh tumor-infiltrating lymphocytes from lung adenocarcinoma.
AU: Roussel-E; Gingras-MC; Grimm-EA; Roth-JA
AD: Department of Thoracic and Cardiovascular Surgery, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
SO: Cancer-Immunol-Immunother. 1995 Jul; 41(1): 1-9
ISSN: 0340-7004
PY: 1995
LA: ENGLISH
CP: GERMANY
AB: Little is known about the activation level of tumor-infiltrating lymphocytes (TIL) in human lung adenocarcinoma. We investigated the activation of fresh TIL at cellular and molecular levels and compared it with autologous and healthy normal peripheral blood lymphocytes (PBL) for baseline level. TIL were extracted from 12 primary lung adenocarcinomas by mechanical disruption without enzyme use and isolated by double-density Ficoll gradients. Flow-cytometry analysis of TIL subset distribution revealed that the majority was composed of T lymphocytes, and double labeling with alpha-CD3 and adhesion/activation markers revealed T cell subsets expressing CD49a, CD49b, CD54, and CD15, each of which was almost absent in autologous T peripheral blood lymphocytes (T-PBL). Moreover, the proportions of T-TIL expressing CD58, CD65, or CD25 were increased severalfold compared to T-PBL. Lymphokine gene activation in TIL was assessed by mRNA reverse transcriptase/polymerase chain reaction (RT-PCR) and primers for interleukin(IL)-2, IL-4, interferon (IFN) gamma, granulocyte/macrophage-colony-stimulating factor (GM-CSF), and tumor necrosis factor (TNF) beta. Semiquantitative comparisons between patients' TIL and PBL and healthy normal and activated PBL were performed by computerized image analysis. RT-PCR gel band products were quantified in relative units as a function of their size and intensity. TIL expressed detectable lymphokine mRNA but seemed poorly activated with respect to the total number of lymphokine genes and the amount of mRNA compared with alpha-CD3-activated healthy PBL. IL-2, IFN gamma, and TNF beta did not appear to be expressed at higher levels in TIL than in autologous or healthy normal PBL. However, two-thirds of the patients had TIL distinguishable from autologous PBL by specific expression of GM-CSF and from healthy normal PBL by expression of IL-4. These results show that lung adenocarcinoma TIL populations had little lymphokine gene activation despite the presence of several T cell subsets expressing different adhesion/activation markers. The lack or deficient combination of lymphokine production may be a factor that prevented efficient activation of TIL in these tumors.
MESH: Gene-Expression-Regulation,-Neoplastic; Immunophenotyping-; Integrins-metabolism; Lymphokines-genetics; Receptors,-Interleukin-2-metabolism; RNA,-Messenger-genetics
MESH: *Adenocarcinoma-immunology; *Cell-Adhesion-Molecules-metabolism; *Lung-Neoplasms-immunology; *Lymphocyte-Transformation; *Lymphocytes,-Tumor-Infiltrating-immunology
TG: Human; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: CA45187CANCI; CA16672CANCI; 1P50CA5820403PP5CANCI
RN: 0; 0; 0; 0; 0
NM: Cell-Adhesion-Molecules; Integrins; Lymphokines; Receptors,-Interleukin-2; RNA,-Messenger
AN: 95368656
UD: 9511
MEDLINE EXPRESS (R) 1991-1995 43 of 125
TI: A hierarchy for integrin expression and adhesiveness among T cell subsets that is linked to TCR gene usage and emphasizes V delta 1+ gamma delta T cell adherence and tissue retention.
AU: Nakajima-S; Roswit-WT; Look-DC; Holtzman-MJ
AD: Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
SO: J-Immunol. 1995 Aug 1; 155(3): 1117-31
ISSN: 0022-1767
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: To define the relationship between T cell phenotype and adhesiveness, we examined T cell adhesion to endothelial cell, fibroblast, and epithelial cell monolayers as well as extracellular matrix proteins (collagen and fibronectin) using a three-color flow cytometry-based adherence assay that minimizes basal adhesion levels and facilitates quantitative lymphocyte subtyping. Regardless of monolayer type, monolayer stimulation conditions, or T cell activation status, we found that the gamma delta-TCR-bearing T cells adhered more efficiently than alpha beta T cells. The difference was based predominantly on increased levels of activatable LFA-1 (and to a lesser degree VLA-4) because: 1) it correlated precisely with inhibitability by anti-LFA-1 (and VLA-4) mAbs and the levels of LFA-1 (and VLA-4) on the cell surface, and 2) it persisted after maximal LFA-1 (and VLA-4) activation with phorbol dibutyrate. In contrast to most cases of alpha beta T cell behavior, gamma delta T cell adhesion to cell monolayers was not linked to memory status, i.e., there was no difference between naive V delta 1+ and memory V delta 2+ populations in levels of LFA-1 (or VLA-4) expression or LFA-1- (or VLA-4-) dependent adhesion to cell monolayers. However, V delta 1+ cells exhibited higher levels of VLA-5 that correlated with an increased adhesiveness to fibronectin and to a 120-kDa fibronectin fragment (FN-120) that contains only the VLA-5-binding domain but not to type I collagen or to a fibronectin fragment (FN-40) that binds only VLA-4. Taken together, the results define a hierarchy for integrin (LFA-1, VLA-4, and VLA-5) expression and consequent adhesion among T cell subsets that is linked to TCR gene usage (but not necessarily linked to memory status) and may thereby help to explain the accumulation and retention of V delta 1+ gamma delta T cells in epithelial and connective tissues.
MESH: Antibodies,-Monoclonal-immunology; Cell-Adhesion; Collagen-metabolism; Endothelium,-Vascular-physiology; Epithelium-physiology; Fibroblasts-physiology; Fibronectins-metabolism; Flow-Cytometry; Gene-Expression-Regulation-drug-effects; Immunologic-Memory; Integrins-physiology; Interleukin-1-pharmacology; Lymphocyte-Function-Associated-Antigen-1-genetics; Receptors,-Antigen,-T-Cell,-alpha-beta-genetics; Receptors,-Antigen,-T-Cell,-alpha-beta-physiology; Receptors,-Antigen,-T-Cell,-gamma-delta-physiology; Receptors,-Fibronectin-genetics; Receptors,-Very-Late-Antigen-genetics; Recombinant-Proteins-pharmacology; T-Lymphocyte-Subsets-drug-effects
MESH: *Gene-Rearrangement,-T-Lymphocyte; *Integrins-biosynthesis; *Lymphocyte-Function-Associated-Antigen-1-biosynthesis; *Receptors,-Antigen,-T-Cell,-gamma-delta-genetics; *Receptors,-Fibronectin-biosynthesis; *Receptors,-Very-Late-Antigen-biosynthesis; *T-Lymphocyte-Subsets-physiology
TG: Comparative-Study; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: HL40078HLNHLBI; HLAI51071HLNHLBI; HL07317HLNHLBI
RN: 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 9007-34-5
NM: Antibodies,-Monoclonal; Fibronectins; Integrins; Interleukin-1; Lymphocyte-Function-Associated-Antigen-1; Receptors,-Antigen,-T-Cell,-alpha-beta; Receptors,-Antigen,-T-Cell,-gamma-delta; Receptors,-Fibronectin; Receptors,-Very-Late-Antigen; Recombinant-Proteins; Collagen
AN: 95363077
UD: 9511
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 44 of 125
TI: Extracellular matrix proteins and leukocyte function.
AU: Pakianathan-DR
AD: Department of Immunology, Genentech Inc., South San Francisco, CA 94080, USA.
SO: J-Leukoc-Biol. 1995 May; 57(5): 699-702
ISSN: 0741-5400
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: Extracellular matrix (ECM) proteins profoundly affect physiological functioning at the cellular level. Cell growth and differentiation, as well as cell shape and migration via the cytoskeleton, are all affected by ECM proteins. Leukocyte interactions with matrices have recently become an exciting field of research because a number of different leukocyte functions are significantly affected by their binding to ECM proteins. This may be especially important in inflammatory responses where leukocytes are primed for inflammatory mediator and cytokine production by binding to ECM proteins during extravasation. Because activated leukocytes produce potentially damaging substances, the progress of an inflammatory response can be profoundly affected by the ECM proteins encountered by leukocytes during their migration from within the peripheral circulation to sites of inflammation. This review summarizes recent publications describing components of the ECM that influence leukocyte function, the receptors involved in leukocyte binding to ECM proteins, and focuses on the effects of ECM proteins on the production of inflammatory mediators and cytokines by human peripheral blood leukocytes.
MESH: Cytokines-physiology; Inflammation-physiopathology; Integrins-physiology; Interleukin-8-biosynthesis; Phagocytosis-; Respiratory-Burst
MESH: *Cell-Adhesion-Molecules-physiology; *Extracellular-Matrix-physiology; *Extracellular-Matrix-Proteins-physiology; *Leukocytes,-Mononuclear-physiology; *Neutrophils-physiology; *Receptors,-Cytoadhesin-physiology
TG: Animal; Human
PT: JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL
RN: 0; 0; 0; 0; 0; 0
NM: Cell-Adhesion-Molecules; Cytokines; Extracellular-Matrix-Proteins; Integrins; Interleukin-8; Receptors,-Cytoadhesin
AN: 95279871
UD: 9509
MEDLINE EXPRESS (R) 1991-1995 45 of 125
TI: In vivo blood monocyte migration to acute inflammatory reactions, IL-1 alpha, TNF-alpha, IFN-gamma, and C5a utilizes LFA-1, Mac-1, and VLA-4. The relative importance of each integrin.
AU: Issekutz-TB
AD: Department of Medicine, University of Toronto, Ontario, Canada.
SO: J-Immunol. 1995 Jun 15; 154(12): 6533-40
ISSN: 0022-1767
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: The role of the monocyte integrins, Mac-1, LFA-1, and VLA-4, on the adhesion of rat blood monocytes to rat microvascular endothelial cells in vitro and the importance of these receptors in monocyte migration to inflammation in vivo were evaluated. Monocyte adhesion to cytokine (IL-1, IFN-gamma, and TNF-alpha)-stimulated endothelial cells was mediated by Mac-1, LFA-1, and VLA-4, but Mac-1 appeared to be less important than LFA-1 or VLA-4. After i.v. injection, large numbers of 51Cr-labeled blood monocytes migrated within 2 h to dermal inflammatory sites induced by C5a, IL-1 alpha, IFN-gamma, TNF-alpha, LPS, and poly inosinic:cytidylic acid. Anti-Mac-1 mAb treatment had no effect, whereas anti-LFA-1 inhibited migration to C5a and the cytokines by 20 to 40%. Blocking both Mac-1 and LFA-1 decreased monocyte accumulation by 50 to 70% to all stimuli. Anti-VLA-4 inhibited monocyte migration to IL-1 alpha, IFN-gamma, TNF-alpha, and LPS, but not to C5a. Combining anti-Mac-1 with anti-VLA-4 did not increase this inhibition, whereas blocking VLA-4 and LFA-1 together further suppressed (60-85%) migration. Combined treatment with mAb to all three integrins inhibited > 98% of the monocyte migration to the inflammatory stimuli. In conclusion: 1) 51Cr blood monocytes can be used to quantify monocyte migration to inflammatory reactions in the rat. 2) Monocytes use Mac-1, LFA-1, and VLA-4 for in vitro adhesion and in vivo migration to cutaneous inflammation, and these integrins are essential for normal migration because blockade of all three virtually abolishes monocyte accumulation. 3) Mac-1 plays a less important role than LFA-1, as LFA-1 appears to substitute for Mac-1, and VLA-4 and LFA-1 can mediate much of the adhesion and migration. 4) The initiating inflammatory stimulus also modifies monocyte integrin usage, supporting the multistep combinatorial model of leukocyte extravasation.
MESH: Antibodies,-Monoclonal-pharmacology; Cell-Adhesion-physiology; Complement-5a-pharmacology; Dermatitis-etiology; Interferon-gamma,-Recombinant-pharmacology; Interleukin-1-pharmacology; Lymphocyte-Function-Associated-Antigen-1-physiology; Macrophage-1-Antigen-physiology; Rats-; Rats,-Inbred-Lew; Receptors,-Very-Late-Antigen-antagonists-and-inhibitors; Receptors,-Very-Late-Antigen-physiology; Recombinant-Proteins-pharmacology; Tumor-Necrosis-Factor-pharmacology
MESH: *Cell-Movement-physiology; *Integrins-physiology; *Monocytes-physiology
TG: Animal; Male; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0; 0; 0; 80295-54-1
NM: Antibodies,-Monoclonal; Integrins; Interferon-gamma,-Recombinant; Interleukin-1; Lymphocyte-Function-Associated-Antigen-1; Macrophage-1-Antigen; Receptors,-Very-Late-Antigen; Recombinant-Proteins; Tumor-Necrosis-Factor; Complement-5a
AN: 95279808
UD: 9509
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 46 of 125
TI: Interleukin-1 alpha stimulates keratinocyte migration through an epidermal growth factor/transforming growth factor-alpha-independent pathway.
AU: Chen-JD; Lapiere-JC; Sauder-DN; Peavey-C; Woodley-DT
AD: Department of Dermatology, Northwestern University School of Medicine, Chicago, IL 60611, USA.
SO: J-Invest-Dermatol. 1995 May; 104(5): 729-33
ISSN: 0022-202X
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) stimulate keratinocyte migration on collagen by up-regulating the alpha 2 subunit of the collagen integrin, alpha 2 beta 1. Interleukin-1 (IL-1) is an autocrine factor, produced by keratinocytes themselves, that is modulated by ultraviolet light and increases the proliferative potential of keratinocytes in culture. The autocrine nature of keratinocyte-derived IL-1 alpha is emphasized by the fact that it induces the keratinocyte to synthesize IL-1 alpha and TGF-alpha, a cytokine known to induce keratinocyte motility. Further, topical application of IL-1 alpha has been shown to promote wound healing in animals. In this study, we used a well-defined keratinocyte migration assay to assess the effect of IL-1 alpha on keratinocyte motility and to examine whether the IL-1 alpha/TGF alpha pathway is involved. The addition of recombinant human IL-1 alpha to keratinocytes produced a statistically significant and concentration-dependent increase in migration on matrices of collagen types I and IV, but not on laminin. Maximal levels of keratinocyte migration obtained on these matrices with IL-1 alpha were comparable to those obtained with stimulation by EGF and TGF-alpha. The effects of TGF-alpha and IL-1 alpha on keratinocyte migration are additive; however, the maximal level of migration achieved by using IL-1 alpha and TGF-alpha in combination never exceeds the maximal level of migration found by using either cytokine alone. The time course of keratinocyte migration induced by IL-1 alpha is delayed (onset of migration 9-12 h after addition) as compared with that induced by TGF-alpha (onset of migration 6-9 h after addition) even if the cells are preincubated in IL-1 alpha. Flow cytometry analysis demonstrated no change in surface expression of integrin subunits, specifically that of integrin subunit alpha 2, previously shown to be up-regulated by EGF/TGF-alpha. These results suggest that IL-1 alpha stimulates keratinocyte migration on collagen via a mechanism distinct from that of EGF/TGF-alpha.
MESH: Cell-Movement-drug-effects; Cell-Movement-physiology; Collagen-ultrastructure; Cytokines-pharmacology; Fibronectins-ultrastructure; Flow-Cytometry; Infant,-Newborn; Integrins-physiology; Time-Factors
MESH: *Epidermal-Growth-Factor-Urogastrone-physiology; *Interleukin-1-pharmacology; *Keratinocytes-cytology; *Transforming-Growth-Factor-alpha-physiology
TG: Human; Male; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: RO1AR33625ARNIAMS; PO1AR41045ARNIAMS
RN: 0; 0; 0; 0; 0; 62229-50-9; 9007-34-5
NM: Cytokines; Fibronectins; Integrins; Interleukin-1; Transforming-Growth-Factor-alpha; Epidermal-Growth-Factor-Urogastrone; Collagen
AN: 95256625
UD: 9508
MEDLINE EXPRESS (R) 1991-1995 47 of 125
TI: Influence of hyposensitization on soluble interleukin-2 receptor, eosinophil cationic protein, in vitro lymphocyte proliferation, in vitro lymphocyte adhesion, and lymphocyte membrane markers in childhood asthma.
AU: Moens-MM; Van-Bever-HP; Stevens-WJ; Mertens-AV; Bridts-CH; De-Clerck-LS
AD: Department of Immunology, Allergology, University of Antwerp, Belgium.
SO: Allergy. 1994 Sep; 49(8): 653-8
ISSN: 0105-4538
PY: 1994
LA: ENGLISH
CP: DENMARK
AB: Soluble interleukin-2 receptor (sIL-2R), eosinophil cationic protein (ECP), the lymphoproliferative response to house-dust mite (HDM), adhesion to human umbilical vein endothelial cells (HUVEC), and lymphocyte membrane markers were studied in three groups of children: healthy children, asthmatic children without hyposensitization (HS), and asthmatic children with HS. HS was associated with significantly lower numbers of peripheral blood eosinophils (PBE) and lower sIL-2R serum levels and with a tendency to lower ECP serum levels and lymphoproliferative response to HDM. There were no changes in the T-lymphocyte phenotypic markers CD4 and CD8 among the three groups. The interleukin-2 receptor (IL-2R, CD25) on HDM-stimulated T lymphocytes increased over unstimulated T lymphocytes in the three groups. The CD25 expression was higher on HDM-stimulated lymphocytes in both asthmatic groups than in healthy children. Adhesion of lymphocytes on HUVEC increased significantly after HDM stimulation in asthmatic children without HS, whereas no change was observed in the two other groups. However, there was no change in the expression of adhesion molecules CD29 and CD11a on lymphocytes in either of the groups. This study provides further evidence that HS can modify lymphocyte and eosinophil functions.
MESH: Adolescence-; Asthma-physiopathology; Asthma-therapy; Cell-Adhesion; Child-; Child,-Preschool; Endothelium,-Vascular-cytology; Flow-Cytometry; Integrins-analysis; Lymphocyte-Function-Associated-Antigen-1-analysis; Lymphocyte-Transformation; Lymphocytes-physiology
MESH: *Antigens,-CD-analysis; *Asthma-immunology; *Blood-Proteins-analysis; *Desensitization,-Immunologic; *Lymphocytes-immunology; *Receptors,-Interleukin-2-analysis
TG: Human
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0
NM: eosinophil-basic-protein; Antigens,-CD; Antigens,-CD29; Blood-Proteins; Integrins; Lymphocyte-Function-Associated-Antigen-1; Receptors,-Interleukin-2
AN: 95382292
UD: 9512
MEDLINE EXPRESS (R) 1991-1995 48 of 125
TI: Natural killer cell function and expression of beta 7 integrin in psoriatic arthritis.
AU: McQueen-FM; Skinner-MA; Krissansen-GW; Robinson-E; Tan-PL
AD: Department of Molecular Medicine, School of Medicine, University of Auckland, New Zealand.
SO: J-Rheumatol. 1994 Dec; 21(12): 2266-73
ISSN: 0315-162X
PY: 1994
LA: ENGLISH
CP: CANADA
AB: OBJECTIVE. To examine the cytotoxic activity of natural killer (NK) cells from peripheral blood (PB) and synovial fluid (SF) of patients with psoriatic arthritis (PsA). The influence of selected inflammatory mediators on the cytolytic function and integrin expression of NK cells was also studied. METHODS. Paired samples of PB and SF lymphocytes (PBL and SFL) were obtained from 8 patients with PsA for comparison of NK activity between PBL and SFL. In 6 patients the phenotype of NK cells was determined by flow cytometry using monoclonal antibodies (Mab) to natural killer associated antigen (NKH-1) and the beta 7 integrin, HML-1 (human mucosal lymphocyte adhesion molecule). RESULTS. NK activity of PB samples was significantly greater than paired SF (p = 0.015). SF NK activity was enhanced by overnight culture with interleukin 2 (IL-2) (p < 0.05). A trend towards reduction of NK activity by prostaglandin E2 (PGE2) was noted (p = 0.06) whereas interleukin 6 (IL-6) and indomethacin had no significant effect. NK activity did not correlate with the percentage of NK cells in PB or SF. However, all SF samples contained a greater proportion of monocytes than PB samples. The expression of HML-1 on NK cells correlated with expression HML-1 on CD3+ cells (r = 0.82) and was greater in SF than PB in PsA and RA patients. Effects of IL-2 on HML-1 expression by NK cells were variable in the 3 patients studied. CONCLUSION. In PsA, HML-1 is an activation marker on NK cells. IL-2 expands or maintains the population of HML-1/NKH1 positive cells and increases NK cytolytic activity. However, cytolytic activity of activated NK cells may be inhibited by monocyte derived PGE2.
MESH: Adult-; Antigens,-CD-analysis; Antigens,-Differentiation,-T-Lymphocyte-analysis; Cells,-Cultured; Dinoprostone-pharmacology; Flow-Cytometry; Indomethacin-pharmacology; Integrins-immunology; Interleukin-2-pharmacology; Interleukin-6-pharmacology; Lymphocyte-Count; Middle-Age; Multivariate-Analysis
MESH: *Arthritis,-Psoriatic-immunology; *Integrins-analysis; *Killer-Cells,-Natural-immunology; *Synovial-Fluid-immunology
TG: Female; Human; Male; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0; 0; 363-24-6; 53-86-1
NM: integrin-alphaEbeta7; integrin-beta7; Antigens,-CD; Antigens,-CD56; Antigens,-Differentiation,-T-Lymphocyte; Integrins; Interleukin-2; Interleukin-6; Dinoprostone; Indomethacin
AN: 95213990
UD: 9507
MEDLINE EXPRESS (R) 1991-1995 49 of 125
TI: Integrin beta 1 cytoplasmic domain dominant negative effects revealed by lysophosphatidic acid treatment.
AU: Smilenov-L; Briesewitz-R; Marcantonio-EE
AD: Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
SO: Mol-Biol-Cell. 1994 Nov; 5(11): 1215-23
ISSN: 1059-1524
PY: 1994
LA: ENGLISH
CP: UNITED-STATES
AB: Integrin receptors localize to focal contact sites and interact with the cytoskeleton via the beta 1 cytoplasmic domain. To study the role of this domain in adhesion, we have expressed in NIH 3T3 cells a cDNA consisting of the interleukin 2 receptor alpha subunit extracellular and transmembrane domains, connected to the integrin beta 1 cytoplasmic domain (IL2R-beta 1). Since the extracellular domain of the chimeric protein has no role in adhesion, this protein could uncouple adhesion from intracellular events. As expected, in a cell line expressing IL2R-beta 1, this chimera was directed to focal contact sites. Unexpectedly, the cells exhibited normal adhesion to fibronectin (FN). However, when a rapid reorganization of the cytoskeleton was induced using lysophosphatidic acid (LPA), IL2R-beta 1 cells detached from FN in contrast to wild-type cells. The detachment in response to LPA could be prevented with cytochalasin D, an inhibitor of actin polymerization. These results imply that a beta 1 cytoplasmic domain, which is uncoupled from adhesion, can compete with the cytoplasmic domain of native integrin beta 1 for cytoskeletal proteins. As a consequence, the IL2R-beta 1 protein acts as a dominant negative effector of adhesion by disrupting the integrin-cytoskeleton connection.
MESH: Actins-metabolism; Chimeric-Proteins-metabolism; Cytochalasin-D-pharmacology; Down-Regulation-Physiology; Fibronectins-metabolism; Gene-Expression; Integrins-genetics; Interleukin-2-metabolism; Mice-; Receptors,-Interleukin-2-metabolism; 3T3-Cells
MESH: *Cell-Adhesion; *Cytoskeleton-metabolism; *Integrins-metabolism; *Lysophospholipids-pharmacology
TG: Animal; Comparative-Study; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: GM44585GMNIGMS
RN: 0; 0; 0; 0; 0; 0; 0; 0; 22144-77-0
NM: Actins; Antigens,-CD29; Chimeric-Proteins; Fibronectins; Integrins; Interleukin-2; Lysophospholipids; Receptors,-Interleukin-2; Cytochalasin-D
AN: 95170118
UD: 9506
MEDLINE EXPRESS (R) 1991-1995 50 of 125
TI: The relative roles of vitronectin receptor, E-selectin and alpha 4 beta 1 in cancer cell adhesion to interleukin-1-treated endothelial cells.
AU: Lafrenie-RM; Gallo-S; Podor-TJ; Buchanan-MR; Orr-FW
AD: Department of Pathology, University of Manitoba, Winnipeg, Canada.
SO: Eur-J-Cancer. 1994; 30A(14): 2151-8
ISSN: 0959-8049
PY: 1994
LA: ENGLISH
CP: ENGLAND
AB: Adhesion of cancer cells to endothelium is thought to be a prerequisite to extravasation during the haematogenous phase of metastasis, and is enhanced after perturbation of the endothelium by interleukin-1 (IL-1). The inducible endothelial adhesion molecules, E-selectin, VCAM-1/alpha 4 beta 1 and vitronectin receptor have been reported to mediate attachment of cancer cells to IL-1-treated endothelial cells. We have examined the relative contribution of these molecules by quantifying the adhesion of a panel of 22 human, 125I-labelled cancer cells and the rat W256 tumour to untreated and IL-1-treated endothelial monolayers in the presence of relevant neutralising antibodies. Antibodies against E-selectin inhibited the adhesion of HL-60 leukaemia cells and two colon carcinomas. Anti-alpha 4 beta 1 antibodies blocked adhesion of four melanomas, five sarcomas and one lung carcinoma. Anti-vitronectin receptor antibodies inhibited adhesion of 14 of the 22 human cell lines to IL-1-treated endothelial cells. Adhesion of seven cell lines was inhibited by more than a single antibody. In contrast, adhesion of one of the cancer cell lines was unaffected by any of the antibodies, suggesting involvement of other IL-1-inducible endothelial adhesion molecules. Moreover, none of the antibodies altered the attachment of cancer cells to unstimulated endothelial monolayers. We conclude that the mechanisms of cancer cell adhesion to the endothelium are influenced by endothelial activation and by the adhesive repertoire of the cancer cell.
MESH: Cell-Adhesion; Endothelium-drug-effects; Interleukin-1-pharmacology; Rats-; Receptors,-Immunologic-physiology; Receptors,-Very-Late-Antigen-physiology
MESH: *Cell-Adhesion-Molecules-physiology; *Integrins-physiology; *Receptors,-Cytoadhesin-physiology; *Tumor-Cells,-Cultured-physiology
TG: Animal; Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0; 0; 0
NM: integrin-alpha4beta1; Cell-Adhesion-Molecules; E-Selectin; Integrins; Interleukin-1; Receptors,-Cytoadhesin; Receptors,-Immunologic; Receptors,-Very-Late-Antigen; Receptors,-Vitronectin
AN: 95161154
UD: 9505
MEDLINE EXPRESS (R) 1991-1995 51 of 125
TI: Regulation of monocyte integrin expression by beta-family chemokines.
AU: Vaddi-K; Newton-RC
AD: Inflammatory Diseases Research, DuPont Merck Pharmaceutical Company, Wilmington, DE 19880.
SO: J-Immunol. 1994 Nov 15; 153(10): 4721-32
ISSN: 0022-1767
PY: 1994
LA: ENGLISH
CP: UNITED-STATES
AB: In the present study we investigated the ability of three monocyte chemokines (MCP-1, MIP-1 alpha, and RANTES) to modulate monocyte adhesion molecules in an attempt to evaluate their potential to induce tissue infiltration of macrophages in vivo. All three chemokines tested induced increased expression of the alpha-chains of two members of beta 2 family of integrins, CD11b and CD11c, and their common beta-chain (CD18). They had no effect on CD11a expression. Enhancement of CD11b and CD11c was dose dependent and followed a distinct time course with peak levels at 4 h. Levels declined to reach basal levels by 24 h. In contrast, IL-1 induced enhancement remained high after 24 h of stimulation. However, the increases caused by chemokines were not mediated by IL-1 as indicated by lack of inhibition by the IL-1R antagonist. Studies on the mechanism of integrin up-regulation showed that mobilization of cytosolic free calcium is an important signaling event in this response and that up-regulation is associated with mobilization from intracellular pools mediated by microtubules. Enhanced CD11b and CD11c expression by chemokines was also found to result in enhancement of monocyte binding to endothelial cells. Further studies indicated that monocyte binding to endothelial cells follows similar dose-response kinetics as the up-regulation of integrins and can be partially blocked by Abs to CD11b and CD11c. These results suggest that modulation of the integrin expression by chemokines may facilitate the tissue trafficking of monocytes during inflammation.
MESH: Calcium-physiology; Cell-Adhesion-physiology; Flow-Cytometry; G-Proteins-physiology; Interleukin-1-physiology; Leukotriene-B4-pharmacology; N-Formylmethionine-Leucyl-Phenylalanine-pharmacology; Platelet-Activating-Factor-pharmacology; Up-Regulation-Physiology-physiology
MESH: *Chemotactic-Factors-physiology; *Cytokines-physiology; *Integrins-biosynthesis; *Monocytes-immunology
TG: Human; In-Vitro
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0; 59880-97-6; 71160-24-2; 7440-70-2
NM: Antigens,-CD18; Chemotactic-Factors; Cytokines; G-Proteins; Integrins; Interleukin-1; Platelet-Activating-Factor; N-Formylmethionine-Leucyl-Phenylalanine; Leukotriene-B4; Calcium
AN: 95052639
UD: 9502
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 52 of 125
TI: A study of CD45RO, CD45RA and CD29 antigen expression on human decidual T cells in an early stage of pregnancy.
AU: Saito-S; Nishikawa-K; Morii-T; Narita-N; Enomoto-M; Ito-A; Ichijo-M
AD: Department of Obstetrics and Gynecology, Nara Medical University, Japan.
SO: Immunol-Lett. 1994 Jun; 40(3): 193-7
ISSN: 0165-2478
PY: 1994
LA: ENGLISH
CP: NETHERLANDS
AB: The decidua is the place where the fertilized egg is implanted and where the immunocompetent cells of the mother come into direct contact with genetically disparate cells of the conceptus. Although the T cells in the decidua are exposed to fetal antigens, the fetus is not rejected by maternal immunocompetent cells. In the present study, we examined surface markers to determine whether the T cells in the human decidua are naive T cells without or memory T cells with a history of antigen stimulation. Although few T cells were present in the decidua, as compared to the peripheral blood, CD45RO+, CD29+ and CD45RA- CD4+ T cells as well as CD45RO+, CD29+ and CD45RA- CD8+ T cells, which are considered to be memory T cells, were in the majority, with only small numbers of CD45RO-, CD29- and CD45RA+ CD4+ and CD8+ cells, which are naive T cells, present. Also, the decidual mononuclear cells secreted IL-2 and IL-4. Since IL-4 is secreted only by memory T cells, it is suggested that in the decidua memory T cells increase in number and secrete cytokines, thereby in some way influencing the phenomenon of fertility.
MESH: CD4-Positive-T-Lymphocytes-immunology; CD8-Positive-T-Lymphocytes-immunology; Flow-Cytometry; Interleukin-2-biosynthesis; Interleukin-4-biosynthesis; Pregnancy-; Pregnancy-Trimester,-First
MESH: *Antigens,-CD-biosynthesis; *Antigens,-CD45-biosynthesis; *Decidua-immunology; *Integrins-biosynthesis; *Interleukins-biosynthesis; *T-Lymphocyte-Subsets-immunology
TG: Female; Human
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0
NM: Antigens,-CD; Antigens,-CD29; Antigens,-CD45; Integrins; Interleukin-2; Interleukin-4; Interleukins
AN: 95048508
UD: 9502
MEDLINE EXPRESS (R) 1991-1995 53 of 125
TI: Synoviocytes in chronic synovitis in situ and cytokine stimulated synovial cells in vitro neo-express alpha 1, alpha 3 and alpha 5 chains of beta 1 integrins.
AU: Rinaldi-N; Barth-T; Henne-C; Mechterscheimer-G; Moller-P
AD: Institute of Pathology, Heidelberg, Germany.
SO: Virchows-Arch. 1994; 425(2): 171-80
ISSN: 0945-6317
PY: 1994
LA: ENGLISH
CP: GERMANY
AB: The expression of the beta 1 integrins was examined immunohistochemically in synoviocytes from normal synovitis membrane and from chronic synovitis of different aetiology and intensity. Normal synoviocytes were alpha 6 beta 1-positive but lacked alpha 1 through alpha 5. In mild inflammation type A synoviocytes neo-expressed alpha 1, alpha 3, and alpha 5 chains. In severe inflammation both type A and B synoviocytes expressed alpha 3, alpha 4, alpha 5, and alpha 6 chains. The effects of inflammatory cytokines, as single agents or in combination, on the beta 1 integrin expression in cultured normal synoviocytes was determined by immunocytochemistry and flow cytometry. The alpha 1 chain, while absent in unstimulated synoviocytes, was induced by interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma). This effect was enhanced by combining IL-1 beta and TNF-alpha. Expression of the alpha 3 chain was up-regulated by IL-1 beta and, more intensely, by IFN-gamma. Transforming growth factor beta (TGF-beta) inhibited the up-regulating effect of IL-1 beta and antagonized the effect of IFN-gamma on alpha 3 chain expression. Expression of the alpha 5 chain was up-regulated significantly by co-stimulation through IL-1 beta together with TGF-beta or TNF-alpha. Thus, the beta 1 integrin profile of cytokine activated synoviocytes in vitro resembled that of synoviocytes in synovitis in situ. These data suggest that IL-1 beta, TNF-alpha, IFN-gamma, and TGF-beta are likely to be among the effectors regulating beta 1 integrin expression in synoviocytes in vivo.
MESH: Cells,-Cultured; Chronic-Disease; Flow-Cytometry; Immunoenzyme-Techniques; Integrins-chemistry; Synovial-Membrane-cytology
MESH: *Cytokines-physiology; *Integrins-biosynthesis; *Synovial-Membrane-immunology; *Synovitis-immunology; *Synovitis-pathology
TG: Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0
NM: Antigens,-CD29; Cytokines; Integrins
AN: 95040233
UD: 9502
MEDLINE EXPRESS (R) 1991-1995 54 of 125
TI: Vascular cell adhesion molecule-1 expressed by peritoneal mesothelium partly mediates the binding of activated human T lymphocytes.
AU: Cannistra-SA; Ottensmeier-C; Tidy-J; DeFranzo-B
AD: Division of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.
SO: Exp-Hematol. 1994 Sep; 22(10): 996-1002
ISSN: 0301-472X
PY: 1994
LA: ENGLISH
CP: UNITED-STATES
AB: Adhesion molecules such as selectins and integrins are known to mediate leukocyte attachment and transmigration through activated vascular endothelium. However, the molecules that mediate subsequent leukocyte entry into nonvascular spaces such as the abdominal cavity during states of peritoneal inflammation have not been identified. Because the peritoneal mesothelial lining represents the final barrier to leukocyte migration into the abdomen, it is likely that adhesion molecules expressed by mesothelial cells are involved in this process. We have developed an in vitro binding assay using confluent layers of normal human mesothelial cells to determine which adhesion molecules might be involved in T lymphocyte-mesothelial recognition. Normal peripheral blood T lymphocytes exhibit low-level specific binding to mesothelium (mean 13% specific binding, n = 4), which is enhanced by phorbol myristate acetate (PMA) treatment (mean 38% specific binding, n = 4). This binding is significantly inhibited in the combined presence of antibodies reactive with CD29 and CD18, suggesting a role for beta 1 and beta 2 integrins, respectively, in this interaction. Interestingly, cultured human mesothelial cells were shown to express vascular cell adhesion molecule-1 (VCAM-1), suggesting that this molecule might function as a counter-receptor for alpha 4 beta 1 expressed by T lymphocytes. Mesothelial cells were also noted to express ICAM-1, CD29, and CD44, but not CD18 or selectins. VCAM-1 expression was not a constitutive property of freshly obtained mesothelial cells but was inducible upon culture in the presence of either interleukin-1 (IL-1), tumor necrosis factor (TNF), or PMA. Neutralizing antibodies reactive with either alpha 4, VCAM-1, or CD29 were all equally capable of inhibiting the binding of activated leukocytes to mesothelial cells (in the presence of anti-CD18 antibody). Mesothelial VCAM-1 was found to have a molecular mass of 110 kD and an mRNA transcript of approximately 3.2 kb, consistent with the predominant VCAM-1 species found in activated endothelium. These data suggest that functional VCAM-1 is expressed on activated mesothelial cells and may play a role in the distal arm of leukocyte trafficking to the abdominal cavity.
MESH: Cell-Adhesion-Molecules-genetics; Cell-Line; Epithelium-chemistry; Integrins-metabolism; Lymphocyte-Transformation; Protein-Binding; RNA,-Messenger-analysis; T-Lymphocytes-metabolism
MESH: *Cell-Adhesion-Molecules-physiology; *Peritoneum-chemistry; *T-Lymphocytes-immunology
TG: Female; Human; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: CA60670CANCI
RN: 0; 0; 0; 0; 126547-89-5
NM: Cell-Adhesion-Molecules; Integrins; RNA,-Messenger; Vascular-Cell-Adhesion-Molecule-1; Intercellular-Adhesion-Molecule-1
AN: 94374503
UD: 9412
MEDLINE EXPRESS (R) 1991-1995 55 of 125
TI: Induction of intercellular adhesion molecule-1 by lipopolysaccharide in canine alveolar macrophages.
AU: Grigg-J; Kukielka-GL; Berens-KL; Dreyer-WJ; Entman-ML; Smith-CW
AD: Speros P. Martel Laboratory, Department of Pediatrics, Methodist Hospital, Houston, Texas.
SO: Am-J-Respir-Cell-Mol-Biol. 1994 Sep; 11(3): 304-11
ISSN: 1044-1549
PY: 1994
LA: ENGLISH
CP: UNITED-STATES
AB: Previous studies have demonstrated that alveolar macrophages (AMphis) adherent to plastic release interleukin-8 in response to lipopolysaccharide (LPS). We sought to determine whether LPS could also alter surface adhesion molecule expression and thus modulate additional AMphi adhesive interactions. Canine AMphis obtained by bronchoalveolar lavage of excised lung were adhered onto tissue culture plastic and exposed to LPS (0.01 to 100 ng/ml). Expression of beta 2 integrins and intercellular adhesion molecule-1 (ICAM-1) was subsequently determined by flow cytometry, a cDNA probe to canine ICAM-1 was used to quantify ICAM-1 mRNA, and changes in adhesion molecule function were assessed by evaluating the extent of homotypic aggregation. ICAM-1 and CD11a/CD18 were present on freshly isolated AMphis. CD11b/CD18 and CD11c/CD18 were expressed at lower levels. Nonadherent AMphis expressed a pattern of beta 2 integrin and ICAM-1 comparable to adherent cells. During short-term LPS stimulation (3 h), adherent AMphis increased both the synthesis and expression of ICAM-1. CD18 expression was either decreased or remained unchanged with LPS stimulation. LPS stimulation in vitro (> 0.01 ng/ml) enhanced the homotypic aggregation of adherent AMphis. Aggregation was blocked by monoclonal antibodies to ICAM-1 (CL18/6) and CD11a (R7.1) and CD18 (R15.7). Similar kinetics were found for expression of ICAM-1 and homotypic aggregation, suggesting that up-regulation of ICAM-1 is a major determinant of the LPS-stimulated aggregation of AMphis.
MESH: Antibodies,-Monoclonal; Bronchoalveolar-Lavage-Fluid-cytology; Cell-Adhesion-Molecules-genetics; Cell-Aggregation-drug-effects; Cells,-Cultured; Dogs-; Integrins-biosynthesis; Receptors,-Leukocyte-Adhesion-biosynthesis; RNA,-Messenger-biosynthesis; Transcription,-Genetic
MESH: *Antigens,-CD-biosynthesis; *Cell-Adhesion-Molecules-biosynthesis; *Lipopolysaccharides-pharmacology; *Macrophages,-Alveolar-metabolism
TG: Animal; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: HL42550HLNHLBI; HL47163HLNHLBI
RN: 0; 0; 0; 0; 0; 0; 0; 0; 0; 126547-89-5
NM: Antibodies,-Monoclonal; Antigens,-CD; Antigens,-CD11; Antigens,-CD18; Cell-Adhesion-Molecules; Integrins; Lipopolysaccharides; Receptors,-Leukocyte-Adhesion; RNA,-Messenger; Intercellular-Adhesion-Molecule-1
AN: 94368496
UD: 9412
MEDLINE EXPRESS (R) 1991-1995 56 of 125
TI: MAb 18D3 triggering of integrin beta 1 will prevent but not terminate proliferation of human T cells.
AU: Teague-TK; McIntyre-BW
AD: Department of Immunology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
SO: Cell-Adhes-Commun. 1994 Jun; 2(2): 169-84
ISSN: 1061-5385
PY: 1994
LA: ENGLISH
CP: SWITZERLAND
AB: Triggering of integrins can deliver signals that will regulate T cell activation and proliferation when coupled with TCR/CD3 signaling. While co-activation stimuli can be achieved either with immobilized natural ligands or immobilized monoclonal antibodies specific for various integrin subunits, counterposing effects can be delivered by ligation of the integrin beta 1 chain (CD29) resulting in the downregulation of T cell proliferation. Thus, integrins may play a pivotal role in cell activation and are involved in both positive and negative regulatory pathways. In this report, anti-beta 1 mAb 18D3 was used to investigate the role of beta 1 in the negative regulation of T cell proliferation. T lymphocytes were stimulated to proliferate when activated with immobilized mAb to CD3 in conjunction with all of a panel of immobilized mAb to different alpha 4 (CD49d) and beta 1 epitopes, except the anti-beta 1.1 mAb 18D3. In soluble form, mAb 18D3 inhibited the induction of DNA synthesis dependent on costimulation of CD3 and the integrin alpha 4 subunit by a mechanism independent of anti-adhesive properties. In kinetic experiments, the addition of mAb 18D3 effectively inhibited the ultimate induction of DNA synthesis at all time points until the time coinciding with the onset of T cell proliferation, indicating that triggering the beta 1.1 epitope may only act to quench activation events prior to cellular commitment to synthesize DNA. MAb 18D3 did not induce cell death nor render cells incompetent for restimulation, but appeared to selectively inhibit IL-2 synthesis with little effect on the induction of IL-2 receptor expression.
MESH: Antibodies,-Monoclonal-pharmacology; Cell-Adhesion; Cell-Division; DNA-biosynthesis; Integrins-immunology; Integrins-physiology; Interleukin-2-biosynthesis; Interleukin-2-pharmacology; Kinetics-; Lymphocyte-Transformation; Signal-Transduction; T-Lymphocytes-cytology
MESH: *Integrins-antagonists-and-inhibitors; *T-Lymphocytes-immunology; *T-Lymphocytes-physiology
TG: Human; In-Vitro; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: CA62596CANCI
RN: 0; 0; 0; 0; 0; 9007-49-2
NM: integrin-alpha4beta1; Antibodies,-Monoclonal; Antigens,-CD29; Integrins; Interleukin-2; DNA
AN: 94363409
UD: 9412
MEDLINE EXPRESS (R) 1991-1995 57 of 125
TI: Ligand binding to monocyte alpha 5 beta 1 integrin activates the alpha 2 beta 1 receptor via the alpha 5 subunit cytoplasmic domain and protein kinase C.
AU: Pacifici-R; Roman-J; Kimble-R; Civitelli-R; Brownfield-CM; Bizzarri-C
AD: Division of Endocrinology and Bone Diseases, Washington University School of Medicine, St. Louis, MO 63110.
SO: J-Immunol. 1994 Sep 1; 153(5): 2222-33
ISSN: 0022-1767
PY: 1994
LA: ENGLISH
CP: UNITED-STATES
AB: Regulation of the functional status of integrin receptors plays a critical role in inflammation and tissue remodeling, as it affects cell adherence and cytokine secretion. We have previously shown that in monocytes the binding of collagen to the alpha 2 beta 1 integrin induces the release of IL-1, an event that is potentiated by binding of fibronectin (Fn) to the alpha 5 beta 1 integrin. In this study, we have investigated the mechanisms leading to this phenomenon. Fn binding to alpha 5 beta 1 induced intracellular signals which increased the alpha 2 beta 1-dependent adhesiveness of monocytes to collagen without modifications of alpha 2 beta 1 expression. By using Abs against the intracellular region of the alpha 5 subunit of the alpha 5 beta 1 receptor, and specific inhibitors of protein kinase C (PKC), we found that the potentiation effect of Fn on monocyte IL-1 production and their adherence to collagen was dependent on an intact alpha 5 subunit cytoplasmic domain, and required PKC activation. Although the alpha 2 beta 1 could be activated by several intracellular second messengers, including protein kinase A and intracellular calcium, the potentiating effect of Fn was mediated only by PKC. These data provide an example of a novel regulatory mechanism: potentiation of beta 1 integrin-mediated events as a result of ligand binding to another integrin of the same class. They also show that the intracellular region of alpha 5 beta 1 plays a critical role in transducing signals generated by ligand binding to alpha 5 beta 1.
MESH: Calcium-physiology; Cell-Adhesion-drug-effects; Cells,-Cultured; Cyclic-AMP-Dependent-Protein-Kinases-physiology; Cytoplasm-physiology; Drug-Synergism; Interleukin-1-secretion; Ligands-; Peptide-Fragments-physiology; Signal-Transduction
MESH: *Fibronectins-metabolism; *Integrins-metabolism; *Integrins-physiology; *Monocytes-metabolism; *Protein-Kinase-C-physiology; *Receptors,-Fibronectin-metabolism
TG: Human; In-Vitro; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: AR39706ARNIAMS; AR41412ARNIAMS
RN: EC 2.7.1.-; EC 2.7.10.-; 0; 0; 0; 0; 0; 0; 0; 7440-70-2
NM: Protein-Kinase-C; Cyclic-AMP-Dependent-Protein-Kinases; collagen-receptor; Fibronectins; Integrins; Interleukin-1; Ligands; Peptide-Fragments; Receptors,-Fibronectin; Calcium
AN: 94327957
UD: 9411
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 58 of 125
TI: Binding and bioeffects of Ipriflavone on a human preosteoclastic cell line.
AU: Benvenuti-S; Petilli-M; Frediani-U; Tanini-A; Fiorelli-G; Bianchi-S; Bernabei-PA; Albanese-C; Brandi-ML
AD: Department of Clinical Physiopathology, University of Florence, School of Medicine, Italy.
SO: Biochem-Biophys-Res-Commun. 1994 Jun 30; 201(3): 1084-9
ISSN: 0006-291X
PY: 1994
LA: ENGLISH
CP: UNITED-STATES
AB: Ipriflavone, a synthetic isoflavone derivative, reduces bone resorption by inhibiting osteoclasts activity. In order to evaluate the role of Ipriflavone on osteoclast growth and differentiation, we tested Ipriflavone and its four "in vivo" main metabolites (Metabolites I, II, III, and V) on a clonal population of human osteoclast precursor cells (FLG 29.1). Pharmacological doses of Ipriflavone and Metabolite III were able to inhibit cell proliferation and interleukin 6 release. In co-cultures of FLG 29.1 cells and osteoblastic (Saos-2) cells Ipriflavone at 1 microM dose inhibited the adhesion of FLG 29.1 cells to the osteoblastic monolayer and reduced the immunocytochemical reaction of the vitronectin receptor. Binding studies with tritiated Ipriflavone showed the presence of a single specific binding site, wtih a Kd of about 70 nM and a binding capacity of 8 fmol/10(6) cells. These results demonstrate a direct effect of Ipriflavone and of Metabolite III on the human osteoclast precursor cell line FLG 29.1.
MESH: Cell-Adhesion-drug-effects; Cell-Differentiation-drug-effects; Cell-Division-drug-effects; Cell-Line; Integrins-metabolism; Interleukin-6-metabolism; Osteoclasts-cytology; Receptors,-Cytoadhesin-metabolism
MESH: *Isoflavones-pharmacology; *Osteoclasts-drug-effects
TG: Female; Human; In-Vitro; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 35212-22-7
NM: Integrins; Interleukin-6; Isoflavones; Receptors,-Cytoadhesin; Receptors,-Vitronectin; Yambolap
AN: 94296373
UD: 9410
MEDLINE EXPRESS (R) 1991-1995 59 of 125
TI: Monocyte rolling, arrest and spreading on IL-4-activated vascular endothelium under flow is mediated via sequential action of L-selectin, beta 1-integrins, and beta 2-integrins.
AU: Luscinskas-FW; Kansas-GS; Ding-H; Pizcueta-P; Schleiffenbaum-BE; Tedder-TF; Gimbrone-MA Jr
AD: Vascular Research Division, Brigham and Women's Hospital, Boston, Massachusetts 02115.
SO: J-Cell-Biol. 1994 Jun; 125(6): 1417-27
ISSN: 0021-9525
PY: 1994
LA: ENGLISH
CP: UNITED-STATES
AB: Leukocyte interactions with vascular endothelium at sites of inflammation can be dynamically regulated by activation-dependent adhesion molecules. Current models, primarily based on studies with polymorphonuclear leukocytes, suggest the involvement of multiple members of the selectin, integrin, and immunoglobulin gene families, sequentially, in the process of initial attachment (rolling), stable adhesion (arrest), spreading and ultimate diapedesis. In the current study, IL-4-activated human umbilical vein endothelium, which selectively expresses VCAM-1 and an L-selectin ligand but not E-selectin, and appropriate function blocking monoclonal antibodies, were used to study monocyte-endothelial interactions in an in vitro model that mimics microcirculatory flow conditions. In this system, L-selectin mediates monocyte rolling and also facilitates alpha 4 beta 1-integrin-dependent arrest, whereas beta 2-integrins are required for spreading of firmly attached monocytes on the endothelial cell surface but not their arrest. These findings provide the first in vitro evidence for human monocyte rolling on cytokine-activated endothelium, and suggest a sequential requirement for both beta 1- and beta 2-integrin-dependent adhesive mechanisms in monocyte-endothelial interactions.
MESH: Antigens,-CD-analysis; Blood-Circulation-physiology; Cell-Adhesion-Molecules-metabolism; Endothelium,-Vascular-drug-effects; Integrins-metabolism; Interleukin-4-pharmacology; Physical-Stimulation
MESH: *Cell-Adhesion-physiology; *Endothelium,-Vascular-physiology; *Monocytes-physiology; *Signal-Transduction
TG: Comparative-Study; Human; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-Non-P.H.S.; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: HL47646HLNHLBI; PO1HL36028HLNHLBI; CA36167CANCI
RN: 0; 0; 0; 0; 0; 0; 0; 0; 126880-86-2
NM: integrin-alpha4beta1; Antigens,-CD; Antigens,-CD18; Antigens,-CD29; Cell-Adhesion-Molecules; Integrins; Interleukin-4; Vascular-Cell-Adhesion-Molecule-1; L-Selectin
AN: 94266971
UD: 9409
MEDLINE EXPRESS (R) 1991-1995 60 of 125
TI: Transmembrane signal transduction by integrin cytoplasmic domains expressed in single-subunit chimeras.
AU: Akiyama-SK; Yamada-SS; Yamada-KM; LaFlamme-SE
AD: Laboratory of Developmental Biology, NIDR, National Institutes of Health, Bethesda, Maryland 20892.
SO: J-Biol-Chem. 1994 Jun 10; 269(23): 15961-4
ISSN: 0021-9258
PY: 1994
LA: ENGLISH
CP: UNITED-STATES
AB: Integrins are heterodimeric, transmembrane cell adhesion receptors that have recently been shown to function in transmembrane signal transduction. To examine the specific role of integrin intracellular domains in signal transduction, chimeric receptors containing various integrin intracellular domains coupled to a reporter consisting of the transmembrane and extracellular domains of the small, non-signaling subunit of the interleukin-2 receptor were expressed in cultured human fibroblasts and assayed for their ability to trigger tyrosine phosphorylation of the 125-kDa cytoplasmic tyrosine kinase, pp125FAK. Tyrosine phosphorylation of pp125FAK was induced in cultured fibroblasts that transiently expressed chimeric receptors containing either the beta 1, beta 3, or beta 5 integrin intracellular domain and were selected by magnetic bead sorting. However, expression of chimeric receptors containing either the alpha 5 or an alternatively spliced form of the beta 3 intracellular domain (beta 3B), as well as those lacking an intracellular domain, failed to induce tyrosine phosphorylation of pp125FAK. These results indicate that information contained in the beta 1, beta 3, or beta 5 integrin intracellular domain is sufficient to stimulate integrin-mediated tyrosine phosphorylation of specific intracellular proteins and that integrin extracellular and transmembrane domains are not required for inducing tyrosine phosphorylation. Our results also indicate that alternative splicing can regulate the ability of beta integrin intracellular domains to participate in signal transduction, and they further suggest that the carboxyl-terminal region of specific beta integrins may play a role in the signal transduction pathway involving extracellular matrix molecules.
MESH: Amino-Acid-Sequence; Cell-Adhesion-Molecules-metabolism; Cells,-Cultured; Chimeric-Proteins; Insulin-Receptor-Protein-Tyrosine-Kinase-metabolism; Molecular-Sequence-Data; Phosphorylation-; Protein-Tyrosine-Kinase-metabolism; Structure-Activity-Relationship
MESH: *Integrins-physiology; *Signal-Transduction-physiology
TG: Human
PT: JOURNAL-ARTICLE
RN: EC 2.7.1.-; EC 2.7.1.-; EC 2.7.1.112; 0; 0; 0; 0; 0; 0
NM: endogenous-substrate-pp120; Insulin-Receptor-Protein-Tyrosine-Kinase; Protein-Tyrosine-Kinase; integrin-beta3; integrin-beta5; Antigens,-CD29; Cell-Adhesion-Molecules; Chimeric-Proteins; Integrins
AN: 94266771
UD: 9409
MEDLINE EXPRESS (R) 1991-1995 61 of 125
TI: Establishment and characterization of cloned human thymic epithelial cell lines. Analysis of adhesion molecule expression and cytokine production.
AU: Fernandez-E; Vicente-A; Zapata-A; Brera-B; Lozano-JJ; Martinez-C; Toribio-ML
AD: Centro de Biologia Molecular Severo Ochoa, Universidad Autonoma de Madrid, Spain.
SO: Blood. 1994 Jun 1; 83(11): 3245-54
ISSN: 0006-4971
PY: 1994
LA: ENGLISH
CP: UNITED-STATES
AB: The thymic stromal microenvironment is required for the generation of immunocompetent T lymphocytes. However, the different thymic stromal cell types have not been fully characterized and their roles regarding T-cell development are not completely understood. To address the phenotypic characteristics of the epithelial component of the human thymic microenvironment as well as its functional involvement in T-cell development, we have established cloned thymic epithelial cell (TEC) lines from fetal and postnatal human thymuses by an explant technique, repeated subculture, and limiting dilution cloning. These cloned TEC lines were shown to be derived from cortical epithelium and to express a number of cell-surface molecules including CD40, major histocompatibility complex (MHC) HLA-ABC and HLA-DR antigens, homing-associated cell-adhesion molecule (H-CAM), intercellular adhesion molecule-1 (ICAM-1), leukocyte function-associated antigen 3 (LFA-3), and beta 1 subfamily integrins. Finally, both postnatal and fetal TEC clones were shown to produce interleukin-1 alpha (IL-1 alpha), IL-6, and IL-7. These well-defined cloned TEC lines may provide useful tools for the study of TEC biology and for the understanding of the precise role played by TEC in human T-cell development.
MESH: Carrier-Proteins-analysis; Cell-Line; Epithelium-cytology; Histocompatibility-Antigens-Class-I-analysis; HLA-DR-Antigens-analysis; Infant-; Integrins-analysis; Receptors,-Cell-Surface-analysis; Receptors,-Lymphocyte-Homing-analysis; Thymus-Gland-chemistry; Thymus-Gland-metabolism
MESH: *Cell-Adhesion-Molecules-analysis; *Cytokines-biosynthesis; *Thymus-Gland-cytology
TG: Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 126547-89-5
NM: Antigens,-CD29; Antigens,-CD44; Carrier-Proteins; Cell-Adhesion-Molecules; Cytokines; Histocompatibility-Antigens-Class-I; HLA-DR-Antigens; Integrins; Receptors,-Cell-Surface; Receptors,-Lymphocyte-Homing; Intercellular-Adhesion-Molecule-1
AN: 94250907
UD: 9409
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 62 of 125
TI: Immunocomplexes stimulate different signalling events to chemoattractants in the neutrophil and regulate L-selectin and beta 2-integrin expression differently.
AU: Molad-Y; Haines-KA; Anderson-DC; Buyon-JP; Cronstein-BN
AD: Department of Medicine, New York University Medical Center, NY 10016.
SO: Biochem-J. 1994 May 1; 299 ( Pt 3): 881-7
ISSN: 0264-6021
PY: 1994
LA: ENGLISH
CP: ENGLAND
AB: Neutrophils express receptors for numerous phlogistons which, when occupied, trigger distinct signal-transduction pathways. Previous studies have shown that stimulation of neutrophils with chemoattractants induces shedding of the adhesive molecule L-selectin and increased expression of the beta 2-integrin CD11b/CD18. We determined the effect of ligation of classic, G-protein-linked chemoattractant receptors [C5a, interleukin-8 (IL-8), formylmethionyl-leucylphenylalanine (FMLP) and substance P], receptors for the Fc portion of IgG (Fc gamma receptors) and receptors for transforming growth factor beta (TGF beta) on expression of adhesive molecules by neutrophils and the stimulus-transduction mechanisms thought to mediate these changes. We were surprised to observe that occupancy of Fc gamma receptors by immunocomplexes (BSA-anti-BSA) stimulated increased expression by neutrophils of CD11b/CD18 at concentrations which did not affect L-selectin expression (EC50 9 micrograms/ml versus 350 micrograms/ml respectively, P < 0.00001, n = 5). In contrast, similar to previous studies, recombinant C5a, recombinant IL-8 and FMLP all stimulated increased expression of CD11b/CD18 (170-260% of basal, P < 0.001, n = 5) and shedding of L-selectin (56-75% reduction from basal, P < 0.001, n = 5) at similar concentrations and with similar potencies (EC50 = 2, 5, and 3 nM respectively). In contrast, neither TGF beta 1 nor, surprisingly, substance P affected expression of CD11b/CD18 or L-selectin. The regulation of expression of CD11b/CD18 or L-selectin in response to FMLP or immunocomplexes was unaffected by cytochalasin B (5 micrograms/ml) or the tyrosine kinase inhibitor tyrphostin-25 (25 microM). Although occupancy of both chemoattractant (FMLP) and Fc gamma receptors stimulated increments in the second messenger diacylglycerol, disruption of actin microfilaments by cytochalasin B enhanced diacylglycerol generation in response to FMLP but not in response to ligation of Fc gamma receptors. Moreover, both FMLP and immune aggregates provoked fluxes of intracellular Ca2+ concentration which differed with respect to both magnitude and kinetics and did not correlate well with regulation of adhesive-molecule expression. As upregulation of CD11b/CD18 is tightly linked to exocytosis of specific granules, these results suggest that shedding of L-selectin by activated neutrophils is not linked to exocytosis. These studies provide further evidence that receptors for chemoattractants and immunocomplexes on the neutrophil are linked to multiple signalling pathways.
MESH: Actins-metabolism; Complement-5a-metabolism; Interleukin-8-metabolism; Phospholipids-metabolism; Receptors,-Fc-metabolism; Substance-P-metabolism; Transforming-Growth-Factor-beta-metabolism
MESH: *Antigen-Antibody-Complex-immunology; *Cell-Adhesion-Molecules-biosynthesis; *Chemotactic-Factors-metabolism; *Integrins-biosynthesis; *Neutrophils-metabolism; *Signal-Transduction
TG: Human; In-Vitro; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: AR11949ARNIAMS; HL19721HLNHLBI
RN: 0; 0; 0; 0; 0; 0; 0; 0; 0; 126880-86-2; 33507-63-0; 80295-54-1
NM: Actins; Antigen-Antibody-Complex; Cell-Adhesion-Molecules; Chemotactic-Factors; Integrins; Interleukin-8; Phospholipids; Receptors,-Fc; Transforming-Growth-Factor-beta; L-Selectin; Substance-P; Complement-5a
AN: 94250256
UD: 9408
MEDLINE EXPRESS (R) 1991-1995 63 of 125
TI: Zymosan-induced IL-8 release from human neutrophils involves activation via the CD11b/CD18 receptor and endogenous platelet-activating factor as an autocrine modulator.
AU: Au-BT; Williams-TJ; Collins-PD
AD: Department of Applied Pharmacology, National Heart & Lung Institute, London, United Kingdom.
SO: J-Immunol. 1994 Jun 1; 152(11): 5411-9
ISSN: 0022-1767
PY: 1994
LA: ENGLISH
CP: UNITED-STATES
AB: We have investigated mechanisms that regulate the generation of IL-8 by human neutrophils on contact with zymosan particles in vitro. Zymosan stimulated IL-8 production, which increased with increasing particle numbers and was abolished by the protein synthesis inhibitor cycloheximide. IL-8 was detectable in culture supernatant at 8 h reaching a maximum at 24 h. In all further experiments IL-8 was measured at 24 h. mAbs to neutrophil CD18 (60.3 and 6.5E) caused a marked suppression of IL-8 generation, but only if added up to 2 h after zymosan stimulation. An anti-CD11b mAb (KIM 225) substantially inhibited zymosan-induced IL-8 release. We investigated whether other mediators generated during phagocytosis modulate IL-8 production. Two selective platelet-activating factor (PAF) receptor antagonists, WEB 2086 and UK 74505, produced a profound suppression of IL-8 generation, when added within 30 min to 1 h of zymosan stimulation. An IL-1R antagonist, a leukotriene B4 antagonist, and an anti-TNF-alpha Ab had no effect on IL-8 generation. FMLP, PAF, and a stable PAF agonist did not stimulate significant IL-8 production, however, a calcium ionophore (A23187) did induce IL-8 release and this was suppressed by UK 74505. We conclude that zymosan-induced IL-8 generation involves stimulation of the neutrophil via a CD11b/CD18 receptor resulting in beta 2-integrin mediated activation of signal transduction mechanisms that leads to cytokine synthesis. Furthermore, endogenously generated PAF, or a PAF, or a PAF-like molecule, appears to have an autocrine function in regulating this pathway of IL-8 production at an early stage after the interaction between the neutrophil and the particles.
MESH: Antibodies,-Monoclonal-immunology; Calcimycin-pharmacology; Integrins-physiology; N-Formylmethionine-Leucyl-Phenylalanine-pharmacology; Sialoglycoproteins-pharmacology; Tetrazoles-pharmacology; Tumor-Necrosis-Factor-physiology
MESH: *Interleukin-8-secretion; *Macrophage-1-Antigen-physiology; *Neutrophils-secretion; *Platelet-Activating-Factor-physiology; *Zymosan-pharmacology
TG: Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 117690-79-6; 52665-69-7; 59880-97-6; 9010-72-4
NM: interleukin-1-receptor-antagonist-protein; Antibodies,-Monoclonal; Antigens,-CD18; Integrins; Interleukin-8; Macrophage-1-Antigen; Platelet-Activating-Factor; Sialoglycoproteins; Tetrazoles; Tumor-Necrosis-Factor; LY-255283; Calcimycin; N-Formylmethionine-Leucyl-Phenylalanine; Zymosan
AN: 94246184
UD: 9408
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 64 of 125
TI: Disparate role of the beta 2-integrin CD18 in the local accumulation of neutrophils in pulmonary and cutaneous inflammation in the rabbit.
AU: Hellewell-PG; Young-SK; Henson-PM; Worthen-GS
AD: Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado.
SO: Am-J-Respir-Cell-Mol-Biol. 1994 Apr; 10(4): 391-8
ISSN: 1044-1549
PY: 1994
LA: ENGLISH
CP: UNITED-STATES
AB: The leukocyte adhesion glycoprotein complex CD11/CD18 has been shown to be important in mediating neutrophil accumulation at sites of inflammation in many experimental models. The exception is the lung, where neutrophil accumulation into the airspaces can be CD18-dependent and -independent, according to the stimulus used to induce pulmonary inflammation. By using the anti-CD18 mAb 60.3, this study examined the role of CD18 on neutrophil accumulation in the lungs of rabbits induced by a local intrabronchial instillation of C5a or interleukin-1 alpha (IL-1 alpha) into the upper lung lobes. For comparison, cutaneous inflammation was induced in the same animals by intradermal injection of the same mediators. Pretreating rabbits with 60.3 abolished accumulation of 111In-labeled neutrophils in skin induced by both C5a and IL-1 alpha. In contrast, in the same animals, C5a-induced accumulation of neutrophils in the lung was not significantly affected by 60.3, while neutrophil accumulation in response to IL-1 alpha showed a significant, but not absolute, dependency on CD18. External gamma scintigraphy of 111In-labeled neutrophils demonstrated that the kinetics of cell retention in the lung was similar for both C5a and IL-1 alpha. In summary, accumulation of neutrophils to sites of inflammation in cutaneous inflammation shows an absolute dependency on CD18, while migration of these cells to sites of inflammation in the lung can be largely independent of this adhesion molecule. These data indicate that the mechanisms responsible for accumulation of neutrophils in cutaneous and pulmonary inflammation are different.
MESH: Antibodies,-Monoclonal-immunology; Bronchoalveolar-Lavage-Fluid-immunology; Complement-5a-immunology; Interleukin-1-immunology; Liver-immunology; Lung-cytology; Lung-immunology; Lung-radionuclide-imaging; Rabbits-; Skin-cytology; Skin-immunology; Spleen-immunology
MESH: *Antigens,-CD-immunology; *Integrins-immunology; *Neutrophils-immunology; *Receptors,-Leukocyte-Adhesion-immunology
TG: Animal; Female; Male; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: HL27353HLNHLBI; HL40784HLNHLBI
RN: 0; 0; 0; 0; 0; 0; 80295-54-1
NM: Antibodies,-Monoclonal; Antigens,-CD; Antigens,-CD18; Integrins; Interleukin-1; Receptors,-Leukocyte-Adhesion; Complement-5a
AN: 94183577
UD: 9406
MEDLINE EXPRESS (R) 1991-1995 65 of 125
TI: Enhanced ICAM-1-dependent adhesion of myelomonocytic cells expressing increased levels of beta 2-integrins and CD43.
AU: Tiisala-S; Majuri-ML; Carpen-O; Renkonen-R
AD: Department of Bacteriology and Immunology, University of Helsinki, Finland.
SO: Scand-J-Immunol. 1994 Mar; 39(3): 249-56
ISSN: 0300-9475
PY: 1994
LA: ENGLISH
CP: ENGLAND
AB: Interaction of ICAM-1 and its ligands plays an important role in the leukocyte binding to endothelium. The best characterized ICAM-ligands belong to the family of beta 2-integrins (CD11/CD18), but recently it has been suggested that CD43, a molecule with no structural resemblance to integrins binds ICAM-1 also. On the leukocytes the main regulatory pathway for ICAM-mediated binding is believed to be a short-term regulation of the avidity of CD11/CD18. In this study the authors investigated whether a quantitative increase in the surface expression of ICAM-ligands also can lead to enhanced binding to purified ICAM-1. PMA-treatment differentiates myelomonocytic cell lines into macrophages with a concomitant increase in the surface expression and mRNA-levels of the beta 2-integrin alpha- and beta-chains as well as that of CD43, another ICAM-ligand. The binding of the PMA-treated THP-1 cells to ICAM-1 was increased simultaneously compared to non-treated cells. The binding was blocked completely with antibodies to CD18 and ICAM-1. It is concluded that in addition to the transient qualitative regulation, a long-term quantitative regulation of ICAM-1 ligands also plays a role in increasing the adhesiveness of myelomonocytic cells. This may be relevant in chronic inflammation episodes.
MESH: Antigens,-CD-genetics; Antigens,-CD-physiology; Antigens,-Surface-physiology; Interferon-Type-II-pharmacology; Interleukin-1-pharmacology; RNA,-Messenger-analysis; Sialoglycoproteins-physiology; Tetradecanoylphorbol-Acetate-pharmacology; Tumor-Cells,-Cultured-chemistry; Tumor-Cells,-Cultured-cytology; Tumor-Necrosis-Factor-pharmacology; Up-Regulation-Physiology-drug-effects
MESH: *Cell-Adhesion-drug-effects; *Cell-Adhesion-Molecules-pharmacology; *Integrins-analysis; *Sialoglycoproteins-analysis
TG: Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 126547-89-5; 16561-29-8; 82115-62-6
NM: sialophorin; Antigens,-CD; Antigens,-CD11; Antigens,-CD18; Antigens,-Surface; Cell-Adhesion-Molecules; Integrins; Interleukin-1; RNA,-Messenger; Sialoglycoproteins; Tumor-Necrosis-Factor; Intercellular-Adhesion-Molecule-1; Tetradecanoylphorbol-Acetate; Interferon-Type-II
AN: 94174233
UD: 9406
MEDLINE EXPRESS (R) 1991-1995 66 of 125
TI: Integrin alpha 4 beta 7 co-stimulation of human peripheral blood T cell proliferation.
AU: Teague-TK; Lazarovits-AI; McIntyre-BW
AD: Department of Immunology, University of Texas M. D. Anderson Cancer, Center, Houston 77030, USA.
SO: Cell-Adhes-Commun. 1994 Dec; 2(6): 539-47
ISSN: 1061-5385
PY: 1994
LA: ENGLISH
CP: SWITZERLAND
AB: The integrin alpha 4 beta 7 mediates lymphocytes adhesion to VCAM-1 on activated endothelium, fibronectin in the extracellular matrix, and the mucosal vascular addressin MAdCAM-1. It is unclear whether alpha 4 beta 7 performs any function beyond directing specific adhesion reactions. We addressed the possibility that triggering of alpha 4 beta 7 with a specific monoclonal antibody was capable of delivering an accessory stimulus that would coactivate T cells and lead to proliferation. At submitogenic levels of anti-CD3 stimulation, triggering of alpha 4 beta 7 by immobilized mAb ACT-1 resulted in T cell blastogenesis, IL-2 production, expression of the IL-2 receptor alpha chain CD25, and ultimately DNA synthesis. These results indicate that the integrin alpha 4 beta 7 is involved in more than lymphocyte adhesion and homing but also plays a role in cell signaling.
MESH: Antibodies,-Monoclonal; Antigens,-CD3-immunology; Integrins-antagonists-and-inhibitors; Interleukin-2-biosynthesis; Kinetics-; Receptors,-Interleukin-2-metabolism
MESH: *Integrins-immunology; *Lymphocyte-Transformation-immunology; *T-Lymphocytes-immunology
TG: Human; In-Vitro; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: CA62596CANCI
RN: 0; 0; 0; 0; 0; 0
NM: lymphocyte-Peyer's-patch-adhesion-molecule; Antibodies,-Monoclonal; Antigens,-CD3; Integrins; Interleukin-2; Receptors,-Interleukin-2
AN: 95261715
UD: 9508
MEDLINE EXPRESS (R) 1991-1995 67 of 125
TI: Interleukin-2 gene-transduced human melanoma cells efficiently stimulate MHC-unrestricted and MHC-restricted autologous lymphocytes.
AU: Arienti-F; Sule-Suso-J; Melani-C; Maccalli-C; Belli-F; Illeni-MT; Anichini-A; Cascinelli-N; Colombo-MP; Parmiani-G
SO: Hum-Gene-Ther. 1994 Sep; 5(9): 1139-50
ISSN: 1043-0342
PY: 1994
LA: ENGLISH
CP: UNITED-STATES
AB: Two human melanoma lines were transduced by a retroviral vector with the gene of the human interleukin-2 (IL-2) and characterized for their immunological properties in comparison with the parental lines. Transduction resulted in the production of biologically active IL-2 in the average amounts of 2,282 and 2,336 pg/ml per 10(5) cells per 24 hr over 3 and 2 months by the Me14932/IL-2 and the Me1B6/IL-2 lines, respectively. Melanoma-transduced cells lost their tumorigenicity in nude mice. No major changes in the phenotype were observed in IL-2 gene-transduced lines. In fact, more than 90% of cells expressed class I and II(DR) HLA, adhesion molecules, integrins, and melanoma-associated antigens. Irradiation with 100-400 Gy, while inhibiting tumor cell growth in vitro, allowed the release of IL-2 by the transduced cells for at least 5 weeks. The two melanoma lines also maintained susceptibility to lysis by lymphokine-activated killer (LAK) cells and by a HLA-A2-restricted melanoma-specific cytotoxic T lymphocyte (CTL) clone recognizing the melanoma antigen (Melan-A). In a limiting dilution assay, transduced, but not parental melanoma lines unless added with an amount of IL-2 comparable to that released by the transduced cells, were able to expand both nonspecific and melanoma-specific CTL precursors from autologous peripheral blood lymphocytes (PBL). In mixed lymphocytes-tumor cultures, IL-2 gene-transduced melanoma cells stimulated the expansion of major histocompatibility complex (MHC)-unrestricted effectors from autologous PBL, and of CD3+ CD8+ MHC-restricted CTL from tumor-invaded lymph nodes. These results indicate that IL-2 gene transduction does not alter significantly the expression of the immunologically relevant molecules of human melanoma lines while increasing their ability to stimulate both specific and nonspecific lymphocyte responses. These lines will be of value in the vaccination of melanoma patients.
MESH: Antigens,-Neoplasm-immunology; Cell-Adhesion-Molecules-metabolism; Cytotoxicity,-Immunologic; DNA,-Complementary-genetics; Gene-Therapy; HLA-A2-Antigen-immunology; Immunophenotyping-; Integrins-metabolism; Interleukin-2-genetics; Interleukin-2-physiology; Killer-Cells,-Lymphokine-Activated-immunology; Lymphocytes,-Tumor-Infiltrating-immunology; Melanoma-therapy; Mice-; Mice,-Nude; Neoplasm-Proteins-metabolism; T-Lymphocytes,-Cytotoxic-immunology; Tumor-Cells,-Cultured-immunology; Tumor-Cells,-Cultured-metabolism
MESH: *HLA-Antigens-immunology; *Interleukin-2-biosynthesis; *Lymphocyte-Transformation; *Melanoma-pathology; *Recombinant-Fusion-Proteins-biosynthesis
TG: Animal; Comparative-Study; Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0; 0; 0; 0
NM: melanoma-specific-protein; Antigens,-Neoplasm; Cell-Adhesion-Molecules; DNA,-Complementary; HLA-Antigens; HLA-A2-Antigen; Integrins; Interleukin-2; Neoplasm-Proteins; Recombinant-Fusion-Proteins
AN: 95134792
UD: 9505
MEDLINE EXPRESS (R) 1991-1995 68 of 125
TI: TGF-beta 1 is a potent inducer of human effector T cells.
AU: Cerwenka-A; Bevec-D; Majdic-O; Knapp-W; Holter-W
AD: Institute of Immunology, VIRCC at SFI, University of Vienna, Austria.
SO: J-Immunol. 1994 Nov 15; 153(10): 4367-77
ISSN: 0022-1767
PY: 1994
LA: ENGLISH
CP: UNITED-STATES
AB: TGF-beta 1 is known to modulate lymphocyte activation affecting cell proliferation and the production of cytokines and Igs. Little is known about the characteristics of T cells grown in the presence of TGF-beta 1. We have stimulated human T cells with PHA in the presence of TGF-beta 1 under serum-free conditions for 7 days and characterized the resulting cell population. TGF-beta 1 (0.0032 to 10 ng/ml) affected neither [3H]thymidine incorporation (day 4) nor cell yield (day 7) in these cultures. However, cells activated in the presence of TGF-beta 1 proliferated vigorously in secondary cultures and produced highly elevated amounts of IL-2 (12 +/- 3-fold enhancement of IL-2 production in response to CD2 plus CD28 stimulation compared with control cells, mean +/- SEM; n = 10). The enhancing effects of TGF-beta 1 were demonstrable over a wide range of concentrations (0.4 to 10 ng/ml). The increased IL-2 protein production was paralleled by a dramatic up-regulation of IL-2 mRNA. In addition, cells precultured with TGF-beta 1 responded with enhanced cluster formation in the secondary cultures. With regard to their phenotype, we observed an increased expression of the alpha E beta 7-integrin human mucosal lymphocyte-1 and of the CD2-restricted epitope CD2R, whereas the expression of CD11a was slightly decreased. In contrast, TGF-beta 1 did not influence the constitutive or activation-induced expression of CD4, CD8, CD45RA, CD45RO, CD25, CD71, CD54, CD58, CD59, and B7. We conclude that TGF-beta 1 supports the generation of human effector cells with a strongly enhanced capacity to respond to subsequent restimulation.
MESH: Antibodies,-Monoclonal; Antigens,-CD-biosynthesis; Antigens,-CD2-biosynthesis; Antigens,-CD2-immunology; Base-Sequence; Blotting,-Northern; Cell-Cycle-immunology; Cells,-Cultured; Flow-Cytometry; Integrins-biosynthesis; Integrins-immunology; Interferon-Type-II-biosynthesis; Interleukin-2-biosynthesis; Molecular-Sequence-Data
MESH: *Lymphocyte-Transformation-immunology; *T-Lymphocytes-immunology; *Transforming-Growth-Factor-beta-immunology
TG: Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0; 82115-62-6
NM: integrin-alphaEbeta7; Antibodies,-Monoclonal; Antigens,-CD; Antigens,-CD2; Integrins; Interleukin-2; Transforming-Growth-Factor-beta; Interferon-Type-II
AN: 95052602
UD: 9502
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 69 of 125
TI: Increased processing of lymphocyte function-associated antigen-1 in human natural killer cells stimulated with IL-2.
AU: Umehara-H; Minami-Y; Domae-N; Bloom-ET
AD: Division of Cellular and Gene Therapies (HFM-518), FDA, Bethesda, MD 20892.
SO: Int-Immunol. 1994 Jul; 6(7): 1071-80
ISSN: 0953-8178
PY: 1994
LA: ENGLISH
CP: ENGLAND
AB: Previously we reported that surface expression of lymphocyte function-associated antigen-1 (LFA-1), the primary leukocyte integrin on human natural killer (NK) and lymphokine-activated killer (LAK) cells, does not differ between NK and LAK cells. In contrast to surface expression, we now report that much higher levels of both precursor and mature forms of LFA-1 molecules were found relative to MHC class I, another membrane glycoprotein, with metabolic labeling of IL-2-stimulated LAK cells compared with native NK cells. An 85-90 kDa glycoprotein, found in much higher quantities in LAK compared with NK cells, appeared to be a precursor of the 95 kDa beta chain of the beta 2 integrin family in human LAK cells because: (i) pulse-chase experiments using LAK cells demonstrated decreased 35S-labeling of the 85-90 kDa molecule with a concomitant increase in the radioactivity of the mature 95 kDa LFA-1 beta chain, (ii) results of protease treatment revealed that the two molecules share virtually identical peptide maps, and (iii) endoglycosaminidase F treatment of LAK cell lysates immunoprecipitated with antibody against LFA-1 beta resulted in the disappearance of both the 85-90 and 96 kDa LFA-1 beta signals, and appearance of a signal at approximately 76 kDa. Digestion of the same immunoprecipitates with neuraminidase resulted in the disappearance of the 95 kDa signal and revealed a single molecular weight signal corresponding to 85-90 kDa. These data suggest that a core protein of approximately 76 kDa becomes N-glycosylated, perhaps terminally with sialic acid residues, to mature into the 95 kDa form. Moreover, the rate of maturation of LFA-1 was more rapid in LAK than NK cells, with half times of 0.8 versus 1.5 h for the alpha chain and 3.7 versus 4.9 h for the beta chain for LAK versus NK cells respectively. IL-2 treatment of NK cells therefore alters the processing of LFA-1 molecules during the transition to LAK cells, providing a larger intracellular reservoir with which to replenish the surface molecule. Together with our previous observation that LFA-1 is phosphorylated and transduces signal more effectively in LAK than NK cells, the findings support the notion that adhesion molecules contribute to the increased function of LAK cells.
MESH: Cells,-Cultured; Electrophoresis,-Polyacrylamide-Gel; Glucosaminidase-pharmacology; Histocompatibility-Antigens-Class-I-biosynthesis; Integrins-biosynthesis; Lymphocyte-Transformation; Neuraminidase-pharmacology; Peptide-Mapping; Protein-Precursors-biosynthesis
MESH: *Interleukin-2-immunology; *Killer-Cells,-Lymphokine-Activated-immunology; *Killer-Cells,-Natural-immunology; *Lymphocyte-Function-Associated-Antigen-1-biosynthesis
TG: Comparative-Study; Human
PT: JOURNAL-ARTICLE
RN: EC 3.2.1.-; EC 3.2.1.18; 0; 0; 0; 0; 0
NM: Glucosaminidase; Neuraminidase; Histocompatibility-Antigens-Class-I; Integrins; Interleukin-2; Lymphocyte-Function-Associated-Antigen-1; Protein-Precursors
AN: 95034459
UD: 9502
MEDLINE EXPRESS (R) 1991-1995 70 of 125
TI: Pentoxifylline inhibits integrin-mediated adherence of interleukin-2- activated human peripheral blood lymphocytes to human umbilical vein endothelial cells, matrix components, and cultured tumor cells.
AU: Kovach-NL; Lindgren-CG; Fefer-A; Thompson-JA; Yednock-T; Harlan-JM
AD: Department of Medicine, University of Washington, Seattle 98195.
SO: Blood. 1994 Oct 1; 84(7): 2234-42
ISSN: 0006-4971
PY: 1994
LA: ENGLISH
CP: UNITED-STATES
AB: Peripheral blood lymphocytes (PBLs) cultured in the presence of recombinant human interleukin-2 (rhIL-2) develop a natural killer (NK) cell phenotype (CD16+, CD56+, CD3-) and are referred to as lymphokine-activated killer cells (LAK). In developing the LAK phenotype, enhanced adherence to matrix components and endothelial cells have been described. In this report we investigated the functional behavior of adhesion receptors in rhIL-2-activated PBLs by in vitro adhesion assay and by flow cytometry. Compared to PBLs, IL-2-activated PBLs had increased integrin-mediated adherence to: (1) fibronectin (FN), (2) human umbilical vein endothelial (HUVE) cells, and (3) cultured melanoma and pancreatic tumor cell lines. This increase in adherence was mediated by increased surface expression of members of the beta 1 and beta 2 integrin subfamilies, as determined by flow cytometric analysis. No induction of an activation-dependent beta 1 (CD29) epitope was detected. We also investigated the effects of the methylxanthine derivative pentoxifylline (PTX) on PBLs and rhIL-2-activated PBL adhesion. PBLs co-cultivated in the presence of rhIL-2 (1,000 U/mL) and PTX exhibited reduced adherence to FN, HUVE and cultured tumor cell lines. This inhibition by PTX was concentration- and time-dependent. The increased expression of integrins induced by rhIL-2 was only in part inhibited by PTX, suggesting that PTX induced a subpopulation of integrins that are expressed but functionally inactive.
MESH: Cell-Adhesion-Molecules-metabolism; Fibronectins-metabolism; Integrins-metabolism; Interleukin-2-pharmacology; Killer-Cells,-Lymphokine-Activated-cytology; Lymphocyte-Transformation-drug-effects; Tumor-Cells,-Cultured
MESH: *Cell-Adhesion-drug-effects; *Endothelium,-Vascular-cytology; *Lymphocytes-cytology; *Pentoxifylline-pharmacology
TG: Human; In-Vitro; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: HL18645HLNHLBI
RN: 0; 0; 0; 0; 6493-05-6
NM: Cell-Adhesion-Molecules; Fibronectins; Integrins; Interleukin-2; Pentoxifylline
AN: 95002934
UD: 9501
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 71 of 125
TI: Glucocorticoids blunt neutrophil CD11b surface glycoprotein upregulation during cardiopulmonary bypass in humans.
AU: Hill-GE; Alonso-A; Thiele-GM; Robbins-RA
AD: Department of Anesthesiology, University of Nebraska Medical Center, Omaha 68198-4455.
SO: Anesth-Analg. 1994 Jul; 79(1): 23-7
ISSN: 0003-2999
PY: 1994
LA: ENGLISH
CP: UNITED-STATES
AB: Neutrophil-endothelial adhesion is the initiating event in neutrophil migration to areas of infection or injury. The binding of neutrophils to endothelium depends upon adhesive glycoproteins, of which the CD11/CD18 glycoproteins are the most important. Because of known upregulation of one of these adhesive glycoproteins (CD11b) during cardiopulmonary bypass (CPB) in humans, we evaluated CD11a, CD11b, and CD11c surface expression before, during, and after CPB in humans, with or without pre-CPB administration of a glucocorticoid (methylprednisolone). Fourteen patients were randomized into two groups: Group S received methylprednisolone (1 g intravenously) 5 min prior to CPB; Group N received no steroid. CD11b was significantly upregulated (P < 0.01) during, and 24 h after, CPB in Group N when compared with controls and Group S at similar time intervals, while in Group S no significant changes were found. Since interleukin-1, tumor necrosis factor, and endotoxin are known to upregulate neutrophil CD11b surface expression and are released during CPB in humans, while steroids are known to suppress the release of these cytokines, the authors conclude that the blunting effect by steroids on CD11b surface expression upregulation during and after CPB in humans is attributed to suppressed cytokine release.
MESH: Cell-Adhesion-Molecules-physiology; Integrins-drug-effects; Integrins-physiology; Methylprednisolone-administration-and-dosage; Middle-Age; Neutrophils-immunology
MESH: *Antigens,-CD-analysis; *Cardiopulmonary-Bypass; *Cell-Adhesion-Molecules-drug-effects; *Methylprednisolone-pharmacology; *Neutrophils-drug-effects; *Up-Regulation-Physiology-drug-effects
TG: Human; Support,-U.S.-Gov't,-Non-P.H.S.
PT: CLINICAL-TRIAL; JOURNAL-ARTICLE; RANDOMIZED-CONTROLLED-TRIAL
RN: 0; 0; 0; 0; 83-43-2
NM: Antigens,-CD; Antigens,-CD11; Cell-Adhesion-Molecules; Integrins; Methylprednisolone
AN: 94279814
UD: 9409
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 72 of 125
TI: Erythrocyte complement receptor type 1 and interactions between immune complexes, neutrophils, and endothelium.
AU: Beynon-HL; Davies-KA; Haskard-DO; Walport-MJ
AD: Rheumatology Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
SO: J-Immunol. 1994 Oct 1; 153(7): 3160-7
ISSN: 0022-1767
PY: 1994
LA: ENGLISH
CP: UNITED-STATES
AB: The deposition of immune complexes (IC) may play an important part in the pathogenesis of vasculitis. An increase in permeability of the vascular endothelial lining is a prerequisite for IC deposition. We used an in vitro model to examine the effects of interactions between IC, neutrophils, and endothelium on the integrity of endothelial cell monolayers. Human umbilical vein endothelial cells were grown to confluence on an FITC-labeled matrix, and monolayer integrity was assessed by the exclusion of an 125I-anti-FITC Ab. Alteration in endothelial monolayer permeability was associated with increased uptake of 125I-anti-FITC Ab, expressed as a percentage of the maximal uptake of Ab onto the FITC-matrix from which endothelial cells had been stripped. Neither resting nor cytokine-stimulated endothelial cells bound hepatitis B surface Ag (HBsAg/anti-HBsAg) IC. Immune complexes were shown to activate neutrophils to induce a 9.5% increase in the permeability of IL-1 beta-stimulated endothelium. This increase in endothelial permeability was abrogated by the addition of RBC bearing normal complement receptor type 1 (CR1) numbers (3.2%). This protective effect was shown to be related to the binding of IC to erythrocyte CR1 and was reduced by CR1 blockade using polyclonal rabbit anti-CR1 Abs. These observations demonstrate that IC are capable of directly activating neutrophils to induce increases in endothelial permeability, which may facilitate the deposition of circulating IC. The results support the hypothesis that the binding of IC to erythrocyte CR1 may inhibit damaging interactions between IC, neutrophils, and endothelium.
MESH: Capillary-Permeability; Cells,-Cultured; Hepatitis-B-Surface-Antigens-immunology; Interleukin-1-pharmacology; Tetradecanoylphorbol-Acetate-pharmacology; Vasculitis-immunology
MESH: *Antigen-Antibody-Complex-metabolism; *Endothelium,-Vascular-physiology; *Erythrocytes-immunology; *Integrins-metabolism; *Neutrophils-immunology
TG: Human; In-Vitro; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 16561-29-8
NM: erythrocyte-immune-adherence-receptor; Antigen-Antibody-Complex; Hepatitis-B-Surface-Antigens; Integrins; Interleukin-1; Tetradecanoylphorbol-Acetate
AN: 94375880
UD: 9412
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 73 of 125
TI: The role of protein tyrosine phosphorylation in integrin-mediated gene induction in monocytes.
AU: Lin-TH; Yurochko-A; Kornberg-L; Morris-J; Walker-JJ; Haskill-S; Juliano-RL
AD: Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill 27599.
SO: J-Cell-Biol. 1994 Sep; 126(6): 1585-93
ISSN: 0021-9525
PY: 1994
LA: ENGLISH
CP: UNITED-STATES
AB: Integrin-mediated cell adhesion, or cross-linking of integrins using antibodies, often results in the enhanced tyrosine phosphorylation of certain intracellular proteins, suggesting that integrins may play a role in signal transduction processes. In fibroblasts, platelets, and carcinoma cells, a novel tyrosine kinase termed pp125FAK has been implicated in integrin-mediated tyrosine phosphorylation. In some cell types, integrin ligation or cell adhesion has also been shown to result in the increased expression of certain genes. Although it seems reasonable to hypothesize that integrin-mediated tyrosine phosphorylation and integrin-mediated gene induction are related, until now, there has been no direct evidence supporting this hypothesis. In the current report, we explore the relationship between integrin-mediated tyrosine phosphorylation and gene induction in human monocytes. We demonstrate that monocyte adherence to tissue culture dishes or to extracellular matrix proteins is followed by a rapid and profound increase in tyrosine phosphorylation, with the predominant phosphorylated component being a protein of 76 kD (pp76). Tyrosine phosphorylation of pp76 and other monocyte proteins can also be triggered by incubation of monocytes with antibodies to the integrin beta 1 subunit, or by F(ab')2 fragments of such antibodies, but not by F(ab) fragments. The ligation of beta 1 integrins with antibodies or F(ab')2 fragments also induces the expression of immediate-early (IE) genes such as IL-1 beta. When adhering monocytes are treated with the tyrosine kinase inhibitors genistein or herbimycin, both phosphorylation of pp76 and induction of IL-1 beta message are blocked in a dose-dependent fashion. Similarly, treatment with genistein or herbimycin can block tyrosine phosphorylation of pp76 and IL-1 beta message induction mediated by ligation of beta 1 integrin with antibodies. These observations suggest that protein tyrosine phosphorylation is an important aspect of integrin-mediated IE gene induction in monocytes. The cytoplasmic tyrosine kinase pp125FAK, although important in integrin signaling in other cell types, seems not to play a role in monocytes because this protein could not be detected in these cells.
MESH: Cell-Adhesion-physiology; Cell-Adhesion-Molecules-metabolism; Cells,-Cultured; Interleukin-1-biosynthesis; Isoflavones-pharmacology; Monocytes-metabolism; Phosphorylation-; Protein-Tyrosine-Kinase-antagonists-and-inhibitors; Protein-Tyrosine-Kinase-metabolism; Quinones-pharmacology
MESH: *Gene-Expression-Regulation-physiology; *Genes,-Immediate-Early; *Integrins-physiology; *Monocytes-physiology; *Phosphoproteins-biosynthesis; *Tyrosine-metabolism
TG: Human; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
RN: EC 2.7.1.-; EC 2.7.1.112; 0; 0; 0; 0; 0; 0; 446-72-0; 55520-40-6; 70563-58-5
NM: endogenous-substrate-pp120; Protein-Tyrosine-Kinase; Cell-Adhesion-Molecules; Integrins; Interleukin-1; Isoflavones; Phosphoproteins; Quinones; genistein; Tyrosine; herbimycin
AN: 94375532
UD: 9412
MEDLINE EXPRESS (R) 1991-1995 74 of 125
TI: Single subunit chimeric integrins as mimics and inhibitors of endogenous integrin functions in receptor localization, cell spreading and migration, and matrix assembly.
AU: LaFlamme-SE; Thomas-LA; Yamada-SS; Yamada-KM
AD: Laboratory of Developmental Biology, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892.
SO: J-Cell-Biol. 1994 Sep; 126(5): 1287-98
ISSN: 0021-9525
PY: 1994
LA: ENGLISH
CP: UNITED-STATES
AB: The ability of single subunit chimeric receptors containing various integrin beta intracellular domains to mimic and/or inhibit endogenous integrin function was examined. Chimeric receptors consisting of the extracellular and transmembrane domains of the small subunit of the human interleukin-2 receptor connected to either the beta 1, beta 3, beta 3B, or beta 5 intracellular domain were transiently expressed in normal human fibroblasts. When expressed at relatively low levels, the beta 3 and beta 5 chimeras mimicked endogenous ligand-occupied integrins and, like the beta 1 chimera (LaFlamme, S. E., S. K. Akiyama, and K. M. Yamada. 1992. J. Cell Biol. 117:437), concentrated with endogenous integrins in focal adhesions and sites of fibronectin fibril formation. In contrast, the chimeric receptor containing the beta 3B intracellular domain (a beta 3 intracellular domain modified by alternative splicing) was expressed diffusely on the cell surface, indicating that alternative splicing can regulate integrin receptor distribution by an intracellular mechanism. Furthermore, when expressed at higher levels, the beta 1 and beta 3 chimeric receptors functioned as dominant negative mutants and inhibited endogenous integrin function in localization to fibronectin fibrils, fibronectin matrix assembly, cell spreading, and cell migration. The beta 5 chimera was a less effective inhibitor, and the beta 3B chimera and the reporter lacking an intracellular domain did not inhibit endogenous integrin function. Comparison of the relative levels of expression of the transfected beta 1 chimera and the endogenous beta 1 subunit indicated that in 10 to 15 h assays, the beta 1 chimera can inhibit cell spreading when expressed at levels approximately equal to the endogenous beta 1 subunit. Levels of chimeric receptor expression that inhibited cell spreading also inhibited cell migration, whereas lower levels were able to inhibit alpha 5 beta 1 localization to fibrils and matrix assembly. Our results indicate that single subunit chimeric integrins can mimic and/or inhibit endogenous integrin receptor function, presumably by interacting with cytoplasmic components critical for endogenous integrin function. Our results also demonstrate that beta intracellular domains, expressed in this context, display specificity in their abilities to mimic and inhibit endogenous integrin function. Furthermore, the approach that we have used permits the analysis of intracellular domain function in the processes of cell spreading, migration and extracellular matrix assembly independent of effects due to the rest of integrin dimers. This approach should prove valuable in the further analysis of integrin intracellular domain function in these and other integrin-mediated processes requiring the interaction of integrins with cytoplasmic components.
MESH: Amino-Acid-Sequence; Base-Sequence; Chimeric-Proteins; DNA-Primers-chemistry; Fibronectins-metabolism; Fluorescent-Antibody-Technique; Molecular-Sequence-Data; Receptors,-Fibronectin-metabolism
MESH: *Cell-Adhesion; *Cell-Movement; *Extracellular-Matrix-ultrastructure; *Integrins-physiology; *Receptor-Aggregation
TG: Human
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0
NM: Chimeric-Proteins; DNA-Primers; Fibronectins; Integrins; Receptors,-Fibronectin
AN: 94342423
UD: 9411
MEDLINE EXPRESS (R) 1991-1995 75 of 125
TI: Expression of early and late activation markers on peripheral blood T lymphocytes does not reliably reflect immune events in transplanted hearts.
AU: Loertscher-R; Forbes-RD; Halabi-G; Lavery-P; Quinn-T
AD: Department of Medicine, Royal Victoria Hospital, Montreal, Quebec, Canada.
SO: Clin-Transplant. 1994 Jun; 8(3 Pt 1): 230-8
ISSN: 0902-0063
PY: 1994
LA: ENGLISH
CP: DENMARK
AB: Monoclonal antibodies directed against early (receptors for interleukin-2 and transferrin [IL-2R, TfR]) and late (PTA1, alpha 1 integrin VLA-1) activation antigens were used as probes to monitor cardiac transplant patients for episodes of acute graft rejection. Age- and sex-matched patient control groups consisting of 11 patients awaiting cardiac transplantation and 13 kidney transplant recipients with long-term grafts, respectively, were used to define an upper limit for normal activation antigen expression (mean + 3 SD) in patients. Expression of all cell markers was significantly higher in both patient control groups than in healthy control individuals. Therefore, the level of activation marker expression in heart patients awaiting transplantation was used as comparison for the patient population under study. Sequential monitoring of 24 heart transplant recipients failed to demonstrate a significant correlation of increased activation marker expression with clinical events of immune activation. Subsequently 62 consecutive endomyocardial biopsy scores in 36 patients were compared with the expression of IL-2R, TfR and VLA-1 on peripheral blood T cells. Neither increased cellular infiltration of the endocardium, nor of the myocardium, was associated with increasing proportions of IL-2R, TfR, or VLA-1 positive T cells. Elevated T-cell expression of the three markers combined indicated acute graft rejection with a sensitivity, specificity, and overall accuracy of 38%, 52%, and 43%, respectively. Acute graft rejection in biopsies with associated myofiber damage (biopsy rejection scores 2 and 3A,B) was not associated with a change in the proportion of activated T cells in circulation within the first 6 months after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)
MESH: Adult-; Antigens,-CD27-genetics; Antigens,-Differentiation,-T-Lymphocyte-genetics; Antigens,-Differentiation,-T-Lymphocyte-immunology; Biopsy-; Blood-; Forecasting-; Gene-Expression; Graft-Rejection-immunology; Heart-Transplantation-pathology; Integrins-genetics; Integrins-immunology; Longitudinal-Studies; Middle-Age; Myocardium-pathology; Receptors,-Interleukin-2-genetics; Receptors,-Interleukin-2-immunology; Receptors,-Transferrin-genetics; Receptors,-Transferrin-immunology; Receptors,-Very-Late-Antigen-genetics; Receptors,-Very-Late-Antigen-immunology
MESH: *Antigens,-CD27-immunology; *Heart-Transplantation-immunology; *Lymphocyte-Transformation-immunology; *T-Lymphocytes-immunology
TG: Comparative-Study; Female; Human; Male; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0
NM: activation-inducer-molecule-antigen; Antigens,-CD27; Antigens,-Differentiation,-T-Lymphocyte; Integrins; Receptors,-Interleukin-2; Receptors,-Transferrin; Receptors,-Very-Late-Antigen
AN: 94339526
UD: 9411
MEDLINE EXPRESS (R) 1991-1995 76 of 125
TI: Tat protein from HIV-1 binds to Mycobacterium avium via a bacterial integrin. Effects on extracellular and intracellular growth.
AU: Denis-M
AD: Pulmonary Research Unit, Faculty of Medicine, University of Sherbrooke, Canada.
SO: J-Immunol. 1994 Sep 1; 153(5): 2072-81
ISSN: 0022-1767
PY: 1994
LA: ENGLISH
CP: UNITED-STATES
AB: We examined the interaction between HIV-1 Tat protein and the opportunistic pathogen Mycobacterium avium. AIDS-associated strains of M. avium were shown to bind Tat protein quite avidly in an attachment assay. The attachment of M. avium to Tat was shown to occur via the integrin alpha 5 beta 1 present on the mycobacterial cell surface. M. avium strains were shown to bind the viral Tat protein with high affinity in a specific fashion (600 binding sites with a Kd of 1 to 5 nM). M. avium coated with Tat protein were shown to be more infective for human alveolar macrophages than untreated M. avium. Other HIV-1 Ags had no such effects (e.g., p24, p17). Examination of the cytokine profile of infected macrophages showed that M. avium-Tat complexes induced higher levels of TGF beta-1 (TGF beta 1) than M. avium alone or M. avium that had been in contact with other viral proteins. Conditioned media from HIV-1-infected H9 cells released a factor that enhanced M. avium intramacrophage growth, and was partially neutralized by an anti-Tat Ab. Finally, Tat protein (purified or present in conditioned media from infected cells) moderately enhanced the growth of M. avium strains in extracellular media, and exposure of M. avium to Tat protein in the presence of IL-6 enhanced the growth of AIDS-associated strains. These data argue for an interaction between the Tat viral product and the opportunistic pathogen M. avium which may contribute to the exquisite susceptibility of AIDS subjects to this pathogen.
MESH: Bacterial-Adhesion; Interleukin-6-pharmacology; Macrophages,-Alveolar-microbiology; Monokines-metabolism; Mycobacterium-avium-metabolism; Transforming-Growth-Factor-beta-pharmacology
MESH: *Acquired-Immunodeficiency-Syndrome-microbiology; *AIDS-Related-Opportunistic-Infections-microbiology; *Gene-Products,-tat-metabolism; *HIV-1-metabolism; *Integrins-metabolism; *Mycobacterium-avium-growth-and-development
TG: Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0
NM: Gene-Products,-tat; Integrins; Interleukin-6; Monokines; Transforming-Growth-Factor-beta
AN: 94327941
UD: 9411
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 77 of 125
TI: Mac-1 (CD11b/CD18) and CD45 mediate the adhesion of hematopoietic progenitor cells to stromal cell elements via recognition of stromal heparan sulfate.
AU: Coombe-DR; Watt-SM; Parish-CR
AD: Sir William Dunn School of Pathology, University of Oxford, UK.
SO: Blood. 1994 Aug 1; 84(3): 739-52
ISSN: 0006-4971
PY: 1994
LA: ENGLISH
CP: UNITED-STATES
AB: Hematopoiesis is regulated by two sets of signals, those generated by cytokines and those generated when precursor cells interact with bone marrow (BM) stroma. The intimate contact between precursors and stroma appears to be mediated by multiple, different receptor-ligand binding events. To identify receptor-ligand pairs mediating the adhesion of hematopoietic precursor cells to stroma, an in vitro model of hematopoiesis was used. This involved coculturing the BM-derived, interleukin-3 (IL-3)-dependent, multipotential cells, FCDP-mix A4 (A4) with a stromal equivalent embryonic mesenchymal cell line, Swiss 3T3 (3T3). In coculture, A4 cells survive, proliferate, and differentiate in the absence of exogenous IL-3, providing they are attached to the 3T3 cell surface. By using detergent lysates of surface-biotinylated A4 cells, A4 cell molecules that bind to the stroma could be detected by either fluorescein isothiocyanate (FITC)-streptavidin or FITC-antibody staining and flow cytometry. Using this approach the beta 2 integrin, Mac-1, and CD45, a receptor-type tyrosine phosphatase, were identified as molecules on the A4 cell surface that bind 3T3 cells. Various glycosaminoglycans (GAGs), particularly heparin and heparan sulfate, blocked binding of A4 cell surface molecules to the 3T3 cells. The binding of CD45 and Mac-1 to the 3T3 cells was similarly blocked by these GAGs. Removal of heparin-binding molecules from A4 cell lysates diminished binding to the 3T3 cells and digestion of the 3T3 cell surface with heparinase abolished the binding of CD45 and Mac-1. The data suggest that heparan sulfate on the 3T3 cell surface is a ligand for both CD45 and Mac-1, but the two molecules recognize different heparan sulfate structural motifs.
MESH: Binding,-Competitive; Bone-Marrow-cytology; Cell-Adhesion; Cells,-Cultured; Ligands-; Mice-; 3T3-Cells
MESH: *Antigens,-CD45-physiology; *Hematopoiesis-; *Hematopoietic-Stem-Cells-cytology; *Heparitin-Sulfate-physiology; *Integrins-physiology; *Macrophage-1-Antigen-physiology
TG: Animal; In-Vitro
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 9050-30-0
NM: Antigens,-CD45; Integrins; Ligands; Macrophage-1-Antigen; Heparitin-Sulfate
AN: 94318948
UD: 9411
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 78 of 125
TI: "Inside-out" signal transduction inhibited by isolated integrin cytoplasmic domains.
AU: Chen-YP; O'Toole-TE; Shipley-T; Forsyth-J; LaFlamme-SE; Yamada-KM; Shattil-SJ; Ginsberg-MH
AD: Department of Vascular Biology, Scripps Research Institute, La Jolla, California 92037.
SO: J-Biol-Chem. 1994 Jul 15; 269(28): 18307-10
ISSN: 0021-9258
PY: 1994
LA: ENGLISH
CP: UNITED-STATES
AB: The affinities of integrin alpha beta heterodimers for extracellular ligands are important regulators of cell adhesion. Intracellular signals provoke changes in the integrin extracellular domain resulting in "activation," as manifested by an increase in affinity. Interactions of integrin cytoplasmic domains with intracellular elements may mediate this "inside-out signaling." Here we report that overexpression of chimeras of the cytoplasmic domain of integrin beta 3 or beta 1 subunits, joined to the extracellular and transmembrane domains of the Tac subunit of the interleukin-2 receptor, reduced integrin affinity. In contrast, chimeras containing the cytoplasmic domain of alpha 5 or alpha IIb or of beta 3 bearing a mutation that disrupts inside-out signaling lacked inhibitory activity. These data suggest that limiting quantities of intracellular factors bind to integrin beta 3 and beta 1 cytoplasmic domains to modulate ligand binding affinity. Structural mimics of these domains may provide a novel means to alter cell adhesion.
MESH: Amino-Acid-Sequence; Base-Sequence; Chimeric-Proteins-biosynthesis; Chimeric-Proteins-pharmacology; Cytoplasm-physiology; CHO-Cells; DNA-Primers; Flow-Cytometry; Hamsters-; Integrins-biosynthesis; Kinetics-; Macromolecular-Systems; Molecular-Sequence-Data; Mutagenesis-; Polymerase-Chain-Reaction; Signal-Transduction-drug-effects; Transfection-
MESH: *Integrins-physiology; *Signal-Transduction-physiology
TG: Animal; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: HL48728HLNHLBI; HL28235HLNHLBI; HL40387HLNHLBI
RN: 0; 0; 0; 0
NM: Chimeric-Proteins; DNA-Primers; Integrins; Macromolecular-Systems
AN: 94308054
UD: 9410
MEDLINE EXPRESS (R) 1991-1995 79 of 125
TI: A fluorescence microassay for the quantitation of integrin-mediated adhesion of neutrophil.
AU: van-Kessel-KP; Park-CT; Wright-SD
AD: Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, NY 10021.
SO: J-Immunol-Methods. 1994 Jun 3; 172(1): 25-31
ISSN: 0022-1759
PY: 1994
LA: ENGLISH
CP: NETHERLANDS
AB: The avidity of leukocyte integrin CR3 (Mac-1, CD11b/CD18, alpha m beta 2) on neutrophils (PMN) may be rapidly modulated by several agonists. We describe a method for determining the avidity of these receptors by measuring the adhesion of PMN to fibrinogen-coated surfaces. Cells are loaded with a succinimidyl ester of carboxyfluorescein diacetate, which is deacetylated by intracellular esterases yielding a highly fluorescent carboxyfluorescein that remains trapped within the PMN. The number of cells adhering to fibrinogen-coated wells of Terasaki microplates is quantitated with a fluorescence plate reader. Stimulation of PMN with a number of agonists, including PMA, fNLLP, Ca-ionophore A23187, interleukin-8, tumor necrosis factor and lipopolysaccharide strongly increased adhesion to fibrinogen, which was CD11b/CD18 dependent. The extent of cell adhesion depended on stimulus concentration and incubation time. This assay requires little time, utilizes small numbers of cells and does not require hazardous reagents.
MESH: Fibrinogen-metabolism; Fluoresceins-; Fluorometry-methods; Macrophage-1-Antigen-physiology; Succinimides-
MESH: *Cell-Adhesion-physiology; *Integrins-physiology; *Neutrophils-physiology
TG: Human; In-Vitro
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 9001-32-5
NM: Fluoresceins; Integrins; Macrophage-1-Antigen; Succinimides; 5-(and-6)-carboxyfluorescein-diacetate-succinimidyl-ester; Fibrinogen
AN: 94267267
UD: 9409
MEDLINE EXPRESS (R) 1991-1995 80 of 125
TI: Inhibition of the transendothelial migration of human T lymphocytes by prostaglandin E2.
AU: Oppenheimer-Marks-N; Kavanaugh-AF; Lipsky-PE
AD: Harold C. Simmons Arthritis Research Center, University of Texas Southwestern Medical Center, Dallas 75235.
SO: J-Immunol. 1994 Jun 15; 152(12): 5703-13
ISSN: 0022-1767
PY: 1994
LA: ENGLISH
CP: UNITED-STATES
AB: To determine whether part of the anti-inflammatory effects of prostaglandin E2 (PGE2) was related to inhibition of T cell interactions with endothelial cells (EC), the effects of PGE2 and other cAMP-elevating agents on the transendothelial migration of human T cells was examined. Although PGE2 did not effect T cell binding to EC, concentration-dependent inhibition of the transendothelial migration of T cells through unstimulated or IL-1-activated EC was observed. PGE2 inhibited the function of both T cells and EC, with maximal inhibition observed when both T cells and EC were treated with PGE2. However, the inhibitory action of PGE2 could not be ascribed to an effect on the adhesion receptor pair, CD11a/CD18-CD54. The inhibitory effect of PGE2 seemed to relate to its capacity to elevate cellular cAMP levels, because 3-isobutyl-1-methylxanthine enhanced PGE2 activity and dibutyryl cAMP and forskolin also inhibited transendothelial migration. The inhibitory effect of PGE2 and the other cAMP-elevating agents on the function of T cells related in part to suppression of their intrinsic locomotory behavior as random migration in the absence of EC was blocked. In EC, PGE2 and the other cAMP-elevating agents increased the barrier function of EC as evidenced by a decrease in the diffusion of [3H]mannitol through the endothelium. These results indicate that part of the anti-inflammatory action of PGE2 relates to its capacity to suppress the transendothelial migration of T cells by cAMP-mediated alterations in the function of both T cells and EC.
MESH: Bucladesine-pharmacology; Cell-Adhesion-drug-effects; Cell-Movement-drug-effects; Cyclic-AMP-metabolism; Diffusion-; Dinoprostone-physiology; Endothelium,-Vascular-cytology; Endothelium,-Vascular-drug-effects; Endothelium,-Vascular-physiology; Forskolin-pharmacology; Inflammation-physiopathology; Integrins-metabolism; Interleukin-1-pharmacology; Lymphocyte-Transformation; Mannitol-pharmacokinetics; T-Lymphocytes-immunology; T-Lymphocytes-physiology
MESH: *Dinoprostone-pharmacology; *T-Lymphocytes-drug-effects
TG: Human; In-Vitro; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: AR09989ARNIAMS; AR39169ARNIAMS
RN: 0; 0; 362-74-3; 363-24-6; 60-92-4; 66428-89-5; 69-65-8
NM: Integrins; Interleukin-1; Bucladesine; Dinoprostone; Cyclic-AMP; Forskolin; Mannitol
AN: 94267175
UD: 9409
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 81 of 125
TI: Adhesion molecules and inflammatory injury.
AU: Albelda-SM; Smith-CW; Ward-PA
AD: Department of Medicine, University of Pennsylvania Medical Center, Philadelphia 19104.
SO: FASEB-J. 1994 May; 8(8): 504-12
ISSN: 0892-6638
PY: 1994
LA: ENGLISH
CP: UNITED-STATES
AB: Neutrophil-endothelial cell interactions are mediated by interacting sets of cell adhesion molecules (CAMs) and chemoattractant/activator molecules to form an "adhesion cascade." The initial phase of inflammation, a transient slowing of neutrophils in postcapillary venules, is mediated by selectins. Subsequently, firm adhesion of neutrophils to the vessel wall occurs via interaction of the CD11/CD18 (beta 2) integrins to endothelial ligands such as intercellular adhesion molecule-1 (ICAM-1). This binding requires activation of CD11/CD18 by exposure of the neutrophil to a variety of activating/chemoattractant molecules, such as platelet-activating factor or interleukin-8. Finally, transmigration into tissues occurs, a process that requires both a chemotactic stimulus and engagement of platelet-endothelial cell adhesion molecule-1 (PECAM-1). Several approaches have been used to probe the role of CAMs in vivo. These include the use of blocking antibodies, chimeric selectin-immunoglobulin proteins, sialyl Lewisx oligosaccharides and peptides, along with the study of humans and animals with genetically determined adhesion deficiencies. These studies demonstrate that CAM blockade can effectively inhibit inflammation; however, there appear to be clear differences in the adhesion requirements for particular types of inflammation. By understanding the CAM/chemoattractant profiles involved in specific disease states, it may be possible to precisely and effectively target therapy to a wide variety of inflammatory diseases.
MESH: Endothelium,-Vascular-physiology; Integrins-; Neutrophils-physiology; Receptors,-Leukocyte-Adhesion; Venules-physiology
MESH: *Cell-Adhesion-physiology; *Cell-Adhesion-Molecules-physiology; *Endothelium,-Vascular-cytology; *Inflammation-; *Leukocytes-physiology; *Venules-cytology
TG: Human; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL
CN: HL49591HLNHLBI; HL46311HLNHLBI; HL31963HLNHLBI
RN: 0; 0; 0
NM: Cell-Adhesion-Molecules; Integrins; Receptors,-Leukocyte-Adhesion
AN: 94237393
UD: 9408
MEDLINE EXPRESS (R) 1991-1995 82 of 125
TI: Suppressed collagen gene expression and induction of alpha 2 beta 1 integrin-type collagen receptor in tumorigenic derivatives of human osteogenic sarcoma (HOS) cell line.
AU: Santala-P; Larjava-H; Nissinen-L; Riikonen-T; Maatta-A; Heino-J
AD: Department of Medical Biochemistry, University of Turku, Finland.
SO: J-Biol-Chem. 1994 Jan 14; 269(2): 1276-83
ISSN: 0021-9258
PY: 1994
LA: ENGLISH
CP: UNITED-STATES
AB: Cell-matrix interactions and intergrin-type cell adhesion receptors are involved in the regulation of tumor cell invasion and metastasis. We have analyzed the expression of matrix proteins and their cellular receptors in human osteosarcoma cells (HOS) and in their virally (KHOS-NP) and chemically (HOS-MNNG) transformed tumorigenic subclones. Transformation decreased dramatically the cellular mRNA levels of alpha 1(I) collagen. Concomitantly with down-regulation of collagen mRNA levels the synthesis of the collagen receptor, alpha 2 beta 1 integrin, was induced. No alpha 2 integrin mRNA was found in HOS cells, suggesting that its expression was regulated most probably at the transcriptional level. 5-Azacytidine alone or combined with alpha 2 integrin-stimulating cytokines, transforming growth factor-beta 1, and interleukin-1 beta, did not turn on the alpha 2 integrin gene. In chemically transformed cells, however, alpha 2 integrin expression could be regulated by cytokines. Thus, we suggest that HOS cells have a strong element, probably other than cell culture-generated de novo promoter methylation, suppressing alpha 2 integrin expression and that this factor is lost in both chemical and viral transformation. Furthermore, the mechanism used by cytokines and malignant transformation to increase alpha 2 integrin expression seems not to be identical. Other transformation-related changes in beta 1 integrins were (i) reduction of the intracellular pool of precursor beta 1 (in HOS-MNNG cells), leading to faster maturation rate of beta 1 subunit and slower maturation rate of alpha subunits, and (ii) decreased electrophoretic mobility of both alpha and beta 1 subunits. At the cellular level both chemical and viral transformation increased cell adhesion to type I collagen.
MESH: Amino-Acid-Sequence; Cell-Adhesion; Cell-Transformation,-Viral; Cytokines-pharmacology; Fibronectins-genetics; Gene-Expression; Laminin-metabolism; Methylation-; Methylnitronitrosoguanidine-; Molecular-Sequence-Data; Peptides-chemistry; Peptides-immunology; Protein-Precursors-metabolism; RNA,-Messenger-genetics; Tumor-Cells,-Cultured
MESH: *Collagen-genetics; *Integrins-metabolism; *Osteosarcoma-genetics
TG: Human; In-Vitro; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0; 0; 70-25-7; 9007-34-5
NM: collagen-receptor; Cytokines; Fibronectins; Integrins; Laminin; Peptides; Protein-Precursors; RNA,-Messenger; Methylnitronitrosoguanidine; Collagen
AN: 94117440
UD: 9404
MEDLINE EXPRESS (R) 1991-1995 83 of 125
TI: Interaction between neutrophils and endothelium.
AU: Elliott-MJ; Finn-AH
AD: Hospital for Sick Children, London, England.
SO: Ann-Thorac-Surg. 1993 Dec; 56(6): 1503-8
ISSN: 0003-4975
PY: 1993
LA: ENGLISH
CP: UNITED-STATES
AB: The endothelial permeability associated with cardiopulmonary bypass in children is due, at least in part, to an inflammatory response. Neutrophils and their relationship with endothelium are fundamental to the production of capillary leak. This review discusses current concepts of the mechanisms involved in adhesion between neutrophils and the endothelium and its control. Evidence for modulation of these changes during bypass in children is reviewed. We have shown that cardiopulmonary bypass in children is associated with down-regulation (or shedding) of L-selectin and up-regulation of expression of CD11b/CD18. There may be a role for the cytokine interleukin-8 in the modulation of this process. We have demonstrated in vitro that certain of the procedures associated with bypass are associated with up-regulation of circulating neutrophil adhesion molecules and with the release of interleukin-8. These factors include changes in temperature and circulation. More research is required to tease out the most important components of the mechanisms of adhesion, and clinical correlations must be defined.
MESH: Capillary-Permeability; Cell-Adhesion-physiology; Cell-Adhesion-Molecules-metabolism; Down-Regulation-Physiology-physiology; Infant-; Infant,-Newborn; Integrins-metabolism; Interleukin-8-physiology; Up-Regulation-Physiology-physiology
MESH: *Cardiopulmonary-Bypass; *Endothelium,-Vascular-metabolism; *Neutrophils-metabolism
TG: Human
PT: JOURNAL-ARTICLE; REVIEW; REVIEW,-ACADEMIC
RN: 0; 0; 0; 126880-86-2
NM: Cell-Adhesion-Molecules; Integrins; Interleukin-8; L-Selectin
AN: 94091905
UD: 9403
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 84 of 125
TI: Intravenous interleukin-8 inhibits granulocyte emigration from rabbit mesenteric venules without altering L-selectin expression or leukocyte rolling.
AU: Ley-K; Baker-JB; Cybulsky-MI; Gimbrone-MA Jr; Luscinskas-FW
AD: Freie Universitat Berlin, Department of Physiology, Germany.
SO: J-Immunol. 1993 Dec 1; 151(11): 6347-57
ISSN: 0022-1767
PY: 1993
LA: ENGLISH
CP: UNITED-STATES
AB: Injection (i.v.) of the granulocyte chemoattractant/activator IL-8 has been shown to reduce neutrophil recruitment into dermal inflammatory sites in vivo. To further investigate the mechanism of this phenomenon, we examined the effect of i.v. [Ser-IL-8]72 (12-20 micrograms/kg) on leukocyte rolling and chemoattractant-induced emigration in mesenteric venules of New Zealand White rabbits and on expression of L-selectin (mAb LAM1-3) and CD18 (mAb 60.3) on circulating rabbit granulocytes. Within 1 min of IL-8 i.v., granulocytes virtually disappeared from carotid blood samples for approximately 5 min. Concomitantly, the flux of rolling leukocytes in mesenteric venules fell from 83 +/- 21 to 2 +/- 1 leukocytes/min. Both rolling leukocyte flux and systemic granulocyte count returned to or exceeded control values within less than 30 min. The chemoattractant/activator FMLP (0.15 microgram/kg i.v.) produced similar results. A second i.v. injection of IL-8 or FMLP, 90 min after the first challenge, had equipotent effects. Local extravascular application of IL-8 via micropipette close to a venule induced adhesion and emigration of 63 +/- 21 leukocytes per site before, but only 26 +/- 9 leukocytes per site 50 to 75 min after i.v. IL-8, when systemic granulocyte count and rolling leukocyte flux had reached or exceeded control values. This was not due to agonist-specific desensitization, because a similar reduction of leukocyte emigration was seen after FMLP i.v. Rabbit granulocytes circulating in vivo uniformly expressed near-control levels of L-selectin at all times between 3 and 360 min after IL-8 i.v. CD18 expression transiently increased after IL-8 i.v. and returned to base line by 90 min. These findings show that IL-8 i.v. reduces granulocyte recruitment to inflammatory sites by inhibiting function(s) necessary for transmigration that are independent of L-selectin and subsequent to rolling.
MESH: Antigens,-CD-analysis; Cell-Adhesion-Molecules-analysis; Cell-Movement-drug-effects; Granulocytes-physiology; Injections,-Intravenous; Integrins-analysis; N-Formylmethionine-Leucyl-Phenylalanine-pharmacology; Rabbits-; Venules-
MESH: *Cell-Adhesion-Molecules-physiology; *Granulocytes-drug-effects; *Interleukin-8-pharmacology
TG: Animal; Male; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: PO1HL36028HLNHLBI; HL47646HLNHLBI; HL45563HLNHLBI
RN: 0; 0; 0; 0; 0; 126880-86-2; 59880-97-6
NM: Antigens,-CD; Antigens,-CD18; Cell-Adhesion-Molecules; Integrins; Interleukin-8; L-Selectin; N-Formylmethionine-Leucyl-Phenylalanine
AN: 94065189
UD: 9403
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 85 of 125
TI: Fibrinogen potentiates the effect of interleukin-3 on early human hematopoietic progenitors.
AU: Zhou-YQ; Levesque-JP; Hatzfeld-A; Cardoso-AA; Li-ML; Sansilvestri-P; Hatzfeld-J
AD: Laboratoire de Biologie Cellulaire et Moleculaire des Facteurs de Croissance, Centre National de la Recherche Scientifique, Villejuif, France.
SO: Blood. 1993 Aug 1; 82(3): 800-6
ISSN: 0006-4971
PY: 1993
LA: ENGLISH
CP: UNITED-STATES
AB: The effect of human fibrinogen on the proliferation of purified SBA- CD34+ human bone marrow progenitors was investigated in clonal cultures. Fibrinogen alone or in combination with erythropoietin had no significant effect. However, in the presence of recombinant human interleukin-3 (IL-3), fibrinogen increased significantly in a dose-dependent manner the number of mixed and burst-forming unit-ethrocyte--derived colonies, whereas the number of other colonies did not significantly change. In the presence of fibrinogen, low concentrations of IL-3 (0.17 U/mL) produced three times more mixed colonies than without fibrinogen, reaching the number of colonies obtained with optimal concentrations of IL-3 (1.67 U/mL). Fibrinogen fragment D had the same effect in the presence of IL-3 as intact fibrinogen, whereas fibrinogen fragment E and human collagen IV did not. This effect was not mediated by integrins, because peptides or monoclonal antibodies that block fibrinogen binding on integrins alpha IIb beta 3, alpha v beta 3 (RGD-peptides), alpha m beta 2 (OKM-1), and alpha x beta 2 (HC1/1) did not affect the observed mitogenic effect. The mitogenic effect of fibrinogen and its D fragment was not mediated by induction of IL-6 or granulocyte--colony-stimulating factor secretion, because it was not inhibited by blocking antisera against these two growth factors. Our results indicate that fibrinogen potentiates the effect of IL-3 on primitive hematopoietic progenitors and suggest that the mitogenic effect of fibrinogen could be mediated via a specific mitogenic receptor that does not belong to the integrin family.
MESH: Amino-Acid-Sequence; Cell-Division-drug-effects; Cells,-Cultured; Drug-Synergism; Erythropoietin-pharmacology; Granulocyte-Colony-Stimulating-Factor-secretion; Integrins-physiology; Interleukin-6-secretion; Molecular-Sequence-Data; Oligopeptides-chemistry; Oligopeptides-pharmacology
MESH: *Bone-Marrow-cytology; *Fibrinogen-administration-and-dosage; *Hematopoiesis-drug-effects; *Hematopoietic-Stem-Cells-drug-effects; *Interleukin-3-administration-and-dosage
TG: Human; In-Vitro; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 11096-26-7; 143011-72-7; 9001-32-5
NM: Integrins; Interleukin-3; Interleukin-6; Oligopeptides; Erythropoietin; Granulocyte-Colony-Stimulating-Factor; Fibrinogen
AN: 93333085
UD: 9311
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 86 of 125
TI: Functional effect of IL-7-enhanced CD19 expression on human B cell precursors.
AU: Wolf-ML; Weng-WK; Stieglbauer-KT; Shah-N; LeBien-TW
AD: Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis 55455.
SO: J-Immunol. 1993 Jul 1; 151(1): 138-48
ISSN: 0022-1767
PY: 1993
LA: ENGLISH
CP: UNITED-STATES
AB: We have previously demonstrated that IL-7 can sustain the growth of normal human B cell precursors (BCP) for several weeks on bone marrow-derived stromal cells. Flow cytometric analysis of BCP recovered from IL-7 supplemented cultures revealed two- to threefold higher levels of cell surface CD19, compared with BCP maintained without IL-7. Short term culture of BCP showed that IL-7 enhancement of CD19 was dose-dependent, with increases detected by day 1 and plateauing by days 3 to 4. IL-7 increased cell-surface CD19 on small lymphoid cells, and to a greater degree on lymphoblasts, whereas cell-surface CD10 was unchanged. The CD34+/CD19+ pro-B cell population showed a greater increase in cell-surface CD19 compared with pre-B and immature B cells. IL-1, IL-3, IL-4, IL-6, and stem-cell factor had no effect on CD19. The potential functional significance of IL-7-enhanced cell-surface CD19 was examined using a F(ab')2 fragment of anti-CD19. This reagent had no effect on [3H]TdR incorporation in BCP cultured in the absence or presence of IL-7 for 5 days, but homotypic adhesion of BCP was induced at a concentration as low as 1.0 ng/ml F(ab')2 anti-CD19. IL-7 enhanced the F(ab')2 anti-CD19 induced homotypic adhesion of BCP in a dose-dependent manner. Blocking antibody studies indicated that members of the beta 1 or beta 2 integrin families did not mediate anti-CD19-induced homotypic adhesion, even though the adhesion was completely ablated by 10 mM EDTA. The pre-B and immature leukemic B cell lines NALM-6 and 1E8 expressed comparable levels of cell-surface CD19, and exhibited comparable increases after IL-7 stimulation. However, their homotypic adhesion responses to anti-CD19 were different. NALM-6 cells exhibited a strong homotypic adhesion response to anti-CD19 that was EDTA-resistant, and beta 1/beta 2 integrin independent. 1E8 cells only responded to anti-CD19 after IL-7 stimulation; this response was EDTA-sensitive and beta 1/beta 2 integrin independent. These collective results indicate that IL-7 not only acts as a growth factor for human BCP, but also regulates signal transduction through cell-surface CD19.
MESH: Antigens,-CD-analysis; B-Lymphocytes-immunology; Bone-Marrow-cytology; Bone-Marrow-embryology; Cell-Adhesion; Cells,-Cultured; Flow-Cytometry; Hematopoiesis-drug-effects; Integrins-metabolism; Tumor-Cells,-Cultured
MESH: *Antigens,-CD-metabolism; *Antigens,-Differentiation,-B-Lymphocyte-metabolism; *B-Lymphocytes-cytology; *Interleukin-7-pharmacology
TG: Human; In-Vitro; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: R01CA31685CANCI; P01CA21737CANCI; U10CA13539CANCI
RN: 0; 0; 0; 0; 0; 0
NM: Antigens,-CD; Antigens,-CD19; Antigens,-CD34; Antigens,-Differentiation,-B-Lymphocyte; Integrins; Interleukin-7
AN: 93315830
UD: 9310
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 87 of 125
TI: Expression of adhesion molecules by human decidual large granular lymphocytes.
AU: Burrows-TD; King-A; Loke-YW
AD: Department of Pathology, University of Cambridge, United Kingdom.
SO: Cell-Immunol. 1993 Mar; 147(1): 81-94
ISSN: 0008-8749
PY: 1993
LA: ENGLISH
CP: UNITED-STATES
AB: This study has examined the expression of adhesion molecules by uterine-specific CD56bright CD16-CD3- large granular lymphocytes using flow cytometry and immunohistology. Data are compared with those obtained after IL-2 stimulation and with peripheral blood CD56+ cells. We have found that decidual CD56bright cells strongly express three fibronectin receptors, alpha 4 beta 1, alpha 5 beta 1, and alpha 4 beta 7. The HML-1 antigen is also expressed. The beta 2 integrins are also found on decidual CD56+ cells although, apart from CD11c, these are present at levels lower than those of corresponding cells in blood. After IL-2 stimulation there is a considerable increase in CD11a/CD18 expression on CD56bright cells. Both ICAM-1 and NCAM are found on CD56bright cells at higher levels compared to those of peripheral blood CD56+ cells. This pattern of expression of beta 1 and beta 2 integrins and members of the immunoglobulin superfamily must have important implications in the behaviour of decidual LGL. These adhesion molecules are also likely to be important in the recruitment and retention of CD56bright LGL in the decidual microenvironment particularly as the specialised decidual extracellular matrix and uterine LGL appear concomitantly at the time of implantation.
MESH: Antigens,-CD3-analysis; Cells,-Cultured-drug-effects; Decidua-immunology; Flow-Cytometry; Gene-Expression-Regulation-immunology; Immunohistochemistry-; Lymphocytes-drug-effects; Pregnancy-; Receptors,-IgG-analysis
MESH: *Antigens,-CD-analysis; *Antigens,-Differentiation,-T-Lymphocyte-analysis; *Cell-Adhesion-Molecules-analysis; *Integrins-analysis; *Interleukin-2-pharmacology; *Lymphocytes-immunology; *Receptors,-Fibronectin-analysis
TG: Female; Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0; 0; 0; 126547-89-5
NM: Antigens,-CD; Antigens,-CD3; Antigens,-CD56; Antigens,-Differentiation,-T-Lymphocyte; Cell-Adhesion-Molecules; Integrins; Interleukin-2; Receptors,-Fibronectin; Receptors,-IgG; Intercellular-Adhesion-Molecule-1
AN: 93215019
UD: 9307
MEDLINE EXPRESS (R) 1991-1995 88 of 125
TI: Effective treatment of the pulmonary fibrosis elicited in mice by bleomycin or silica with anti-CD-11 antibodies.
AU: Piguet-PF; Rosen-H; Vesin-C; Grau-GE
AD: Department of Pathology, University of Geneva, Switzerland.
SO: Am-Rev-Respir-Dis. 1993 Feb; 147(2): 435-41
ISSN: 0003-0805
PY: 1993
LA: ENGLISH
CP: UNITED-STATES
AB: We treated two types of experimental pulmonary fibrosis elicited in mice by the intratracheal instillation of bleomycin or silica with monoclonal antibodies (mAbs) specific for the leukocytic integrins CD-11a or CD-11b. This treatment completely prevented collagen deposition, as measured by lung hydroxyproline content on Day 15 after instillation. Furthermore, anti CD-11a mAb was also effective when given on Days 20 and 25 and the lung hydroxyproline content determined on Day 30 after instillation, i.e., in the treatment of an established pulmonary fibrosis. Histologic studies indicated that anti CD-11 mAbs attenuated the fibrosing alveolitis induced by silica or bleomycin and in addition markedly decreased the lymphoid infiltration and platelet microthrombi associated with both types of alveolitis. In contrast, these mAbs had little or no effect on the cellularity of the bronchoalveolar lavage, mainly composed of macrophages. In normal mice, anti CD-11 mAbs also decreased the number of interstitial lymphocytes and the lung collagen content. These observations may lead new to therapies for pulmonary fibrosis.
MESH: Antibody-Specificity; Bleomycin-; Blotting,-Northern; Bronchoalveolar-Lavage-Fluid-cytology; Drug-Screening; Interleukin-1-analysis; Lung-chemistry; Lung-pathology; Mice-; Mice,-Inbred-CBA; Mice,-Inbred-C57BL; Pulmonary-Fibrosis-chemically-induced; Pulmonary-Fibrosis-pathology; RNA,-Messenger-analysis; Silicon-Dioxide; Tumor-Necrosis-Factor-analysis
MESH: *Antibodies,-Monoclonal-therapeutic-use; *Integrins-immunology; *Pulmonary-Fibrosis-therapy
TG: Animal; Comparative-Study; Male; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 11056-06-7; 7631-86-9
NM: Antibodies,-Monoclonal; Integrins; Interleukin-1; RNA,-Messenger; Tumor-Necrosis-Factor; Bleomycin; Silicon-Dioxide
AN: 93159004
UD: 9305
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 89 of 125
TI: Expression of integrins and examination of their adhesive function in normal and leukemic hematopoietic cells.
AU: Liesveld-JL; Winslow-JM; Frediani-KE; Ryan-DH; Abboud-CN
AD: Hematology Unit, University of Rochester Medical Center, NY 14642.
SO: Blood. 1993 Jan 1; 81(1): 112-21
ISSN: 0006-4971
PY: 1993
LA: ENGLISH
CP: UNITED-STATES
AB: Adhesion of hematopoietic progenitor cells to marrow-derived adherent cells has been noted for erythroid, myeloid, and lymphoid precursors. In this report, we have characterized very late antigen (VLA) integrin expression on normal CD34+ marrow progenitors, on leukemic cell lines, and on blasts from patients with acute myelogenous or monocytic leukemias. CD34+ progenitor cells expressed the integrin beta 1 chain (CD29), VLA-4 alpha (CD49d), and VLA-5 alpha (CD49e). The myeloid lines KG1 and KG1a also expressed CD49d and CD49e as did the Mo7e megakaryoblastic line. CD29, CD18, and CD11a were also present on each of these cell lines. Only the Mo7e line expressed the cytoadhesins GPIIbIIIa or GPIb. Binding of KG1a to marrow stroma was partially inhibited by antibodies to CD49d and its ligand, vascular cell adhesion molecule (VCAM-1). The majority of leukemic blasts studied expressed CD49d and CD49e as well. Blasts from patients with acute myelomonocytic leukemia consistently bound to stroma at levels greater than 20%, and adhesion to stroma could in some cases be partly inhibited by anti-CD49d. No role for glycosylphosphatidyl-inositol (GPI)-linked structures was demonstrated in these binding assays because the adhesion of leukemic blasts to stroma was not diminished after treatment with phosphatidylinositol-specific phospholipase C (PI-PLC). These studies indicate that CD34+ myeloid progenitors, myeloid leukemic cell lines, and leukemic blasts possess a similar array of VLA integrins. Their functional importance individually or in combination with other mediators of attachment in adhesion, transendothelial migration, and differentiation has yet to be fully elucidated.
MESH: Antibodies-; Antigens,-CD-analysis; Granulocyte-Macrophage-Colony-Stimulating-Factor-pharmacology; Granulocytes-physiology; Immunophenotyping-; Interleukin-3-pharmacology; Leukemia,-Monocytic,-Acute-metabolism; Leukemia,-Monocytic,-Acute-pathology; Leukemia,-Myelocytic,-Acute-metabolism; Leukemia,-Myelocytic,-Acute-pathology; Tumor-Cells,-Cultured
MESH: *Bone-Marrow-cytology; *Cell-Adhesion-physiology; *Hematopoietic-Stem-Cells-physiology; *Integrins-physiology; *Leukemia-pathology
TG: Human; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: K11HL0238501A1HLNHLBI; HL18208HLNHLBI; CA32737CANCI
RN: 0; 0; 0; 0; 0; 83869-56-1
NM: Antibodies; Antigens,-CD; Antigens,-CD34; Integrins; Interleukin-3; Granulocyte-Macrophage-Colony-Stimulating-Factor
AN: 93112942
UD: 9304
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 90 of 125
TI: Fibroblasts increase adhesion to neutrophils after stimulation with phorbol ester and cytokines.
AU: Giuliani-AL; Spisani-S; Cavalletti-T; Reali-E; Melchiorri-L; Ferrari-L; Lanza-F; Traniello-S
AD: Istituto di Chimica Biologica, Universita degli Studi di Ferrara, Italy.
SO: Cell-Immunol. 1993 Jun; 149(1): 208-22
ISSN: 0008-8749
PY: 1993
LA: ENGLISH
CP: UNITED-STATES
AB: In our research there was spontaneous adhesion between resting fibroblasts and neutrophils in vitro which could be increased by stimulating either the coculture of cells or each cell type separately with various stimulants. Interferon-gamma, interleukin-1, and interleukin-6 significantly increased adhesion; however, the highest adhesive response was obtained when cocultures were treated with phorbol myristate acetate (PMA). As PMA-stimulated fibroblasts show the highest adhesion to resting neutrophils, it was suggested that adhesion was primarily due to an effect on fibroblasts. Without Mg2+ PMA did not stimulate fibroblast adhesion, whereas in the absence of Ca2+ the response was only partially reduced. Spontaneous adhesion was independent of both neutrophil integrins and fibroblast ICAM-1, whereas cytokine-stimulated adhesion was blocked by mAbs against ICAM-1; PMA-stimulated adhesion was not affected by mAbs anti-ICAM-1, but was partially inhibited by mAbs anti-beta 2 integrins. These results suggested the presence of mechanisms able to modulate the adhesive fibroblast-neutrophil interaction in inflammatory and wound healing processes.
MESH: Calcium-pharmacology; Cations,-Divalent; Cell-Adhesion-Molecules-metabolism; Cell-Adhesion-Molecules-physiology; Flow-Cytometry; Integrins-physiology; Magnesium-pharmacology
MESH: *Cell-Adhesion-drug-effects; *Cytokines-pharmacology; *Fibroblasts-cytology; *Neutrophils-cytology; *Tetradecanoylphorbol-Acetate-pharmacology
TG: Human; In-Vitro; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 126547-89-5; 16561-29-8; 7439-95-4; 7440-70-2
NM: Cations,-Divalent; Cell-Adhesion-Molecules; Cytokines; Integrins; Intercellular-Adhesion-Molecule-1; Tetradecanoylphorbol-Acetate; Magnesium; Calcium
AN: 93292094
UD: 9309
MEDLINE EXPRESS (R) 1991-1995 91 of 125
TI: Phorbol ester-induced degranulation in adherent human eosinophil granulocytes is dependent on CD11/CD18 leukocyte integrins.
AU: Egesten-A; Gullberg-U; Olsson-I; Richter-J
AD: Department of Medicine, University of Lund, Sweden.
SO: J-Leukoc-Biol. 1993 Mar; 53(3): 287-93
ISSN: 0741-5400
PY: 1993
LA: ENGLISH
CP: UNITED-STATES
AB: Secretion of unique eosinophil granule constituents may play a role in allergic and parasitic reactions. Therefore we have investigated possible mechanisms for regulation of secretion in eosinophils. A hemolytic plaque assay and an enzyme-linked immunospot (ELISPOT) assay were developed for detection of secreted eosinophil cationic protein (ECP) from single adherent eosinophils. The protein kinase C activator phorbol 12-myristate 13-acetate (PMA) induced release of ECP in a dose-dependent fashion but 4-alpha-PMA, an analogue that does not activate protein kinase C, did not cause degranulation. Staurosporine and K252a, inhibitors of protein kinase C, decreased PMA-induced ECP secretion. Low concentrations of cytochalasin B enhanced PMA-induced secretion but high concentrations had an inhibitory effect. The calcium ionophores A23187 and ionomycin were weaker secretagogues than PMA. Tumor necrosis factor, granulocyte-macrophage colony-stimulating factor, interleukin-3, interleukin-5, N-formylmethionyl-leucyl-phenylalanine, and lipopolysaccharide caused little or no degranulation in adherent eosinophils. Preincubation of eosinophils with antibodies to CD18, the common beta chain of leukocyte adhesion proteins, resulted in inhibition of PMA-induced ECP release from adherent cells. 1,2-Bis(O-aminophenyl)-ethane-ethane-N,N,N',N'-tetraacetic acid (BAPTA), an agent that acts intracellularly by chelation of calcium, also inhibited PMA-mediated ECP release. In conclusion, PMA induces release of ECP from single adherent eosinophils and the effect appears to be mediated via protein kinase C and, in contrast to that in neutrophils, to be dependent on CD11/CD18 leukocyte integrins.
MESH: Antibodies-pharmacology; Antigens,-CD-immunology; Antigens,-CD-pharmacology; Blood-Proteins-antagonists-and-inhibitors; Blood-Proteins-secretion; Calcimycin-pharmacology; Cell-Adhesion; Chelating-Agents-pharmacology; Cytochalasin-B-pharmacology; Egtazic-Acid-analogs-and-derivatives; Egtazic-Acid-pharmacology; Eosinophils-cytology; Granulocyte-Macrophage-Colony-Stimulating-Factor-pharmacology; Integrins-drug-effects; Interleukin-3-pharmacology; Ionomycin-pharmacology; Lipopolysaccharides-pharmacology; N-Formylmethionine-Leucyl-Phenylalanine-pharmacology; Protein-Kinase-C-antagonists-and-inhibitors; Tetradecanoylphorbol-Acetate-pharmacology; Tumor-Necrosis-Factor-pharmacology
MESH: *Cell-Degranulation-drug-effects; *Eosinophils-physiology; *Phorbol-Esters-pharmacology
TG: Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: EC 2.7.1.-; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 139890-68-9; 14930-96-2; 16561-29-8; 52665-69-7; 56092-81-0; 59880-97-6; 67-42-5; 83869-56-1
NM: Protein-Kinase-C; eosinophil-basic-protein; Antibodies; Antigens,-CD; Antigens,-CD11; Antigens,-CD18; Blood-Proteins; Chelating-Agents; Integrins; Interleukin-3; Lipopolysaccharides; Phorbol-Esters; Tumor-Necrosis-Factor; 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic-acid-acetoxymethyl-ester; Cytochalasin-B; Tetradecanoylphorbol-Acetate; Calcimycin; Ionomycin; N-Formylmethionine-Leucyl-Phenylalanine; Egtazic-Acid; Granulocyte-Macrophage-Colony-Stimulating-Factor
AN: 93203746
UD: 9306
MEDLINE EXPRESS (R) 1991-1995 92 of 125
TI: Adhesion of human myeloma-derived cell lines to bone marrow stromal cells stimulates interleukin-6 secretion.
AU: Uchiyama-H; Barut-BA; Mohrbacher-AF; Chauhan-D; Anderson-KC
AD: Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115.
SO: Blood. 1993 Dec 15; 82(12): 3712-20
ISSN: 0006-4971
PY: 1993
LA: ENGLISH
CP: UNITED-STATES
AB: Previous studies show that human myeloma-derived cell lines specifically adhere to fibronectin (FN) through very late antigen-4 (VLA-4; alpha 4 beta 1 integrin complex) and RGD-peptide mechanisms, which may contribute to the localization of tumor cells in bone marrow (BM). In these studies, we characterized the adhesion of myeloma-derived cell lines to both normal and myeloma BM stromal cells (BMSCs) and the effect of adhesion on DNA synthesis. Because interleukin-6 (IL-6) plays an important role in the pathogenesis of multiple myeloma, we also examined the effects of tumor cell adhesion on IL-6 secretion by BMSCs. In 51chromium binding assays, the U266, ARH-77, and IM-9 cell lines showed 52% +/- 12%, 55% +/- 6%, and 47% +/- 7% specific adherence, respectively, to normal BMSCs and 74% +/- 4%, 60% +/- 3%, and 61% +/- 6% specific adherence, respectively, to myeloma BMSCs. In contrast, only 12% to 13% specific binding of HS-Sultan cells to BMSCs was noted. The binding of myeloma cells to BMSCs was partially blocked with anti-beta 1 monoclonal antibody (MoAb), anti-beta 2 integrin MoAb, and excess RGD peptide, suggesting multiple mechanisms for the adhesion of myeloma cell lines to BMSCs. Binding of cell lines to FN or myeloma BMSCs did not affect cell line proliferation; however, adhesion of myeloma cell lines to normal BMSCs decreased DNA synthesis, ie, stimulation indices are 0.1 +/- 0.04, 0.2 +/- 0.1, 0.2 +/- 0.07, and 0.1 +/- 0.06 for the adherent non-IL-6-dependent U266, ARH-77, HS-Sultan, and IM-9 cells, respectively (n = 5, P < .01). In contrast, adherence of IL-6-dependent B9 cells increased their proliferation (stimulation index, 3.2 +/- 0.7). Significant (twofold to eightfold) increases in IL-6 secretion were evident in cell line-adherent (> or = 12 hours) normal and myeloma BMSC cultures. Paraformaldehyde fixation of BMSCs before adhesion completely abrogated IL-6 secretion, suggesting that IL-6 secretion was triggered in BMSCs rather than in cell lines. Partial blocking of cell line adhesion to BMSCs, using anti-beta 1 integrin and anti-beta 2 integrin MoAbs and RGD peptide, also partially blocked the triggering of IL-6 secretion by BMSCs. When cell lines were placed in Transwell inserts and then cultured with either normal or myeloma BMSCs, permitting juxtaposition without cell to cell contact between myeloma cell lines and BMSCs, no increase in IL-6 secretion was observed.(ABSTRACT TRUNCATED AT 400 WORDS)
MESH: Antibodies,-Monoclonal-pharmacology; Bone-Marrow-cytology; Bone-Marrow-physiopathology; Cell-Division-drug-effects; Cell-Line; Culture-Media,-Conditioned; Fibronectins-; Integrins-immunology; Integrins-physiology; Tumor-Cells,-Cultured
MESH: *Bone-Marrow-physiology; *Cell-Adhesion; *Interleukin-6-biosynthesis; *Multiple-Myeloma-pathology; *Multiple-Myeloma-physiopathology
TG: Human; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: CA50947CANCI
RN: 0; 0; 0; 0; 0
NM: Antibodies,-Monoclonal; Culture-Media,-Conditioned; Fibronectins; Integrins; Interleukin-6
AN: 94083652
UD: 9403
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 93 of 125
TI: T-cell receptor heterogeneity of gamma delta T-cell clones from human female reproductive tissues.
AU: Christmas-SE; Brew-R; Deniz-G; Taylor-JJ
AD: Department of Immunology, Royal Liverpool University Hospital, U.K.
SO: Immunology. 1993 Mar; 78(3): 436-43
ISSN: 0019-2805
PY: 1993
LA: ENGLISH
CP: ENGLAND
AB: gamma delta T cells were isolated from human decidua parietalis, decidua basalis and cervix and cloned in the presence of interleukin-2 (IL-2). T-cell receptor (TcR) expression was then analysed and compared with that of a panel of gamma delta T-cell clones from peripheral blood. Only 17/40 (42.5%) clones from decidua parietalis were V gamma 9+/V delta 2+ as compared to 68/94 (72%) of peripheral blood clones (P < 0.005). Conversely, 50% of clones from decidua parietalis but only 15% of clones from peripheral blood were V delta 1+ (P < 0.001). At least seven distinct TcR types were identified among the panel of clones from decidua parietalis and at least six different types were expressed by the panel of 17 clones from cervix. This receptor heterogeneity was not a result of interdonor variation as in all instances where more than one clone was obtained from a single sample, individual clones having between two and five receptor types were identified. However, 23/24 (95.8%) of clones from decidua basalis were V gamma 9+/V delta 2+. Most clones from decidua parietalis and cervix, whether V gamma 9+/V delta 2+ or V delta 1+, were positive for the mucosal lymphocyte marker, HML-1, but expression was often heterogeneous within a single clone. In contrast, almost all gamma delta T-cell clones from peripheral blood were HML-1-. Thus, unlike the mouse, gamma delta T cells within these human female reproductive tissues have a diverse TcR repertoire which, in decidua parietalis, is distinct from that of peripheral blood.
MESH: Antigens,-Neoplasm-analysis; Blotting,-Southern; Clone-Cells-immunology; Gene-Rearrangement,-delta-Chain-T-Cell-Antigen-Receptor-immunology; Gene-Rearrangement,-gamma-Chain-T-Cell-Antigen-Receptor-immunology; Integrins-analysis; Polymerase-Chain-Reaction; Pregnancy-; Receptors,-Antigen,-T-Cell,-gamma-delta-genetics
MESH: *Cervix-Uteri-immunology; *Decidua-immunology; *Receptors,-Antigen,-T-Cell,-gamma-delta-analysis
TG: Female; Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0
NM: integrin-alphaEbeta7; Antigens,-Neoplasm; Integrins; Receptors,-Antigen,-T-Cell,-gamma-delta
AN: 93239213
UD: 9307
MEDLINE EXPRESS (R) 1991-1995 94 of 125
TI: Expression of integrins and other adhesion molecules on NK cells; impact of IL-2 on short- and long-term cultures.
AU: Maenpaa-A; Jaaskelainen-J; Carpen-O; Patarroyo-M; Timonen-T
AD: Department of Pathology, University of Helsinki, Finland.
SO: Int-J-Cancer. 1993 Mar 12; 53(5): 850-5
ISSN: 0020-7136
PY: 1993
LA: ENGLISH
CP: UNITED-STATES
AB: We have investigated, using flow cytometry, the expression of 19 adhesion molecules on fresh and IL-2-activated NK cells. The study included beta 1, beta 2 and beta 3 integrins, CD2, CD54 and CD58 (belonging to the immunoglobulin superfamily), and CD44 and L-selectin (homing receptors). alpha 1 and alpha 2 of the beta 1 integrins were non-existent and alpha 3 was weak on freshly isolated NK cells, but their expression increased after 4 weeks in culture with IL-2. On the other hand, some down-regulation of alpha 4 and alpha 5 and disappearance of alpha 6 was detected. CD 11a/CD18 was upregulated by IL-2, whereas CD11b-c/CD18 were down-regulated. As a novel finding we detected beta 3 on IL-2-activated T and NK cells. CD2, CD44, CD54 and CD58 were increased by IL-2 but L-selectin was strongly down-regulated on the long-term-activated NK cells. Although IL-2-activated lymphocytes are potent tumor-lysing killer cells in vitro and therefore a potential modality in cancer treatment, the IL-2 induced changes in lymphocyte adhesion molecule expression may also lead to undesired effects, such as altered untargeted distribution and compromised migratory capacity.
MESH: Flow-Cytometry; Interleukin-2-pharmacology; Killer-Cells,-Natural-drug-effects
MESH: *Cell-Adhesion-Molecules-analysis; *Integrins-analysis; *Killer-Cells,-Natural-chemistry
TG: Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0
NM: Cell-Adhesion-Molecules; Integrins; Interleukin-2
AN: 93194403
UD: 9306
MEDLINE EXPRESS (R) 1991-1995 95 of 125
TI: Adhesion proteins on human microglial cells and modulation of their expression by IL1 alpha and TNF alpha.
AU: Sebire-G; Hery-C; Peudenier-S; Tardieu-M
AD: Laboratoire de Neurovirologie et Neuroimmunologie, Universite Paris XI, UFR Kremlin-Bicetre.
SO: Res-Virol. 1993 Jan-Feb; 144(1): 47-52
ISSN: 0923-2516
PY: 1993
LA: ENGLISH
CP: FRANCE
AB: Expression of adhesion proteins on human microglial cells was studied by immunocytochemistry. Both microglial cells and peripheral blood monocytes expressed beta 2 integrins and molecules of the immunoglobulin superfamily at similar levels whereas the expression of the beta 1 integrins (alpha 2-VLA (very late antigen), alpha 4-VLA, alpha 5-VLA, alpha 6-VLA) was higher on microglial cells than on monocytes. Stimulation of microglial cells with interleukin-1 alpha and tumour necrosis factor-alpha, the main cytokines detected in HIV1-infected central nervous system (CNS), increased the microglial expression of alpha 1-VLA, intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and beta 2-LFA-1 (leukocyte-function-associated molecule-1) but not of alpha L-LFA-1. Such an induction of adhesion molecules could facilitate penetration of HIV1-infected monocytes into brain parenchyma and their adhesion to CNS cells, and could maintain a chronic inflammation during human immunodeficiency virus-1 (HIV1) encephalopathy.
MESH: Cells,-Cultured; Macrophages-drug-effects; Monocytes-drug-effects
MESH: *Brain-cytology; *Immunoglobulins-metabolism; *Integrins-metabolism; *Interleukin-1-pharmacology; *Macrophages-metabolism; *Monocytes-metabolism; *Tumor-Necrosis-Factor-pharmacology
TG: Comparative-Study; Human
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0
NM: Immunoglobulins; Integrins; Interleukin-1; Tumor-Necrosis-Factor
AN: 93189885
UD: 9306
MEDLINE EXPRESS (R) 1991-1995 96 of 125
TI: Post-translational processing of the leukocyte integrin alpha 4 beta 1.
AU: Bednarczyk-JL; Szabo-MC; McIntyre-BW
AD: Department of Immunology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
SO: J-Biol-Chem. 1992 Dec 15; 267(35): 25274-81
ISSN: 0021-9258
PY: 1992
LA: ENGLISH
CP: UNITED-STATES
AB: The leukocyte integrin alpha 4 beta 1 (VLA-4, CD49d/CD29) is a receptor for the extracellular matrix protein fibronectin and the endothelial adhesion protein VCAM-1. We have analyzed the biosynthesis and post-translational modifications of the two subunits of this receptor complex. The alpha 4 subunit was initially synthesized as a single-chain polypeptide that underwent the formation of complex endoglycosidase H-resistant oligosaccharide side chains and which could be proteolytically cleaved into two noncovalently associated fragments. The level and rate of alpha 4 subunit cleavage was dependent on the cell studied. The T cell tumor line HPB-ALL expressed both intact and fragmented alpha 4 on the cell surface. The interleukin-2-dependent natural killer line NK 3.3 and long term interleukin-2-dependent activated T lymphocytes cleaved the alpha 4 polypeptide earlier and more efficiently than did HPB-ALL cells and did not have detectable levels of intact alpha 4 on the cell surface. The proteolysis of alpha 4 was blocked by treating cells with either the lysosomotrophic amine NH4Cl or the carboxylic ionophore monensin. The presence of complex N-linked oligosaccharides did not seem to be necessary for alpha 4 cleavage or for binding of the alpha 4 beta 1 complex to a synthetic peptide corresponding to the binding site for this receptor on fibronectin.
MESH: Amino-Acid-Sequence; Antibodies,-Monoclonal; Epitopes-analysis; Fibronectins-metabolism; Glycoside-Hydrolases-antagonists-and-inhibitors; Immunoblotting-; Integrins-genetics; Interleukin-2-pharmacology; Leukemia,-Lymphocytic,-Acute; Macromolecular-Systems; Molecular-Sequence-Data; Peptides-chemical-synthesis; Peptides-immunology; Protease-Inhibitors-pharmacology; Receptors,-Very-Late-Antigen-genetics; T-Lymphocytes-drug-effects; T-Lymphocytes-immunology; Tumor-Cells,-Cultured
MESH: *Integrins-biosynthesis; *Leukocytes-physiology; *Protein-Processing,-Post-Translational; *Receptors,-Very-Late-Antigen-biosynthesis
TG: Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: EC 3.2.1.; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0
NM: Glycoside-Hydrolases; integrin-alpha4beta1; Antibodies,-Monoclonal; Epitopes; Fibronectins; Integrins; Interleukin-2; Macromolecular-Systems; Peptides; Protease-Inhibitors; Receptors,-Very-Late-Antigen
AN: 93094239
UD: 9303
MEDLINE EXPRESS (R) 1991-1995 97 of 125
TI: L-selectin function is required for beta 2-integrin-mediated neutrophil adhesion at physiological shear rates in vivo.
AU: Von-Andrian-UH; Hansell-P; Chambers-JD; Berger-EM; Torres-Filho-I; Butcher-EC; Arfors-KE
AD: La Jolla Institute for Experimental Medicine, California 92037.
SO: Am-J-Physiol. 1992 Oct; 263(4 Pt 2): H1034-44
ISSN: 0002-9513
PY: 1992
LA: ENGLISH
CP: UNITED-STATES
AB: In vivo interactions between neutrophils and endothelial cells (EC) follow a multistep process involving two distinct neutrophil adhesion receptors. L-selectin, constitutively functional on resting neutrophils, mediates an activation-independent primary interaction resulting in rolling along the venular wall. Subsequent activation of rolling neutrophils induces upregulation and functional activation of beta 2-integrins (CD11/CD18) leading to firm attachment. Based on previous findings we hypothesized that, under shear force, rolling may be essential for successful neutrophil-EC recognition. Here we report results of our studies of human neutrophil behavior in interleukin (IL)-1-activated rabbit mesentery venules, an interaction that requires both L-selectin and beta 2-integrins. Rolling of human neutrophils is L-selection mediated; it was strongly reduced by monoclonal antibody inhibition or enzymatic removal of L-selectin. Furthermore, activation induced L-selectin shedding and, in a dose- and time-dependent fashion, rendered neutrophils unable to recognize inflamed EC despite expression of active beta 2-integrins, which promoted adhesion in vitro. Neutrophils activated for 5 min or longer lost most of their ability to roll. However, 1-3 min after activation, rolling was reduced (not abolished), and cells that were still able to roll displayed a significant tendency for a CD18-dependent transition from rolling to sticking. The whole sequence of events, rolling, sticking, and transendothelial migration, could be observed if an extravascular chemotactic stimulus was applied by superfusing mesenteries with leukotriene B4. Under such conditions, sticking and emigration was blocked when rolling was inhibited by enzymatic removal of L-selectin. Our results indicate that primary neutrophil interaction with inflamed EC through the L-selectin is a prerequisite for neutrophil function at physiological shear rates in vivo.
MESH: Antibodies,-Monoclonal-immunology; Cell-Adhesion; Cell-Adhesion-Molecules-immunology; Child,-Preschool; Chymotrypsin-pharmacology; Hemodynamics-drug-effects; Interleukin-1-pharmacology; Leukotriene-B4-pharmacology; Microcirculation-drug-effects; Perfusion-; Splanchnic-Circulation-drug-effects; Stress,-Mechanical
MESH: *Cell-Adhesion-Molecules-physiology; *Integrins-physiology; *Neutrophils-physiology
TG: Human; Male; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: AI19957AINIAID; GM37734GMNIGMS
RN: EC 3.4.21.1; 0; 0; 0; 0; 126880-86-2; 71160-24-2
NM: Chymotrypsin; Antibodies,-Monoclonal; Cell-Adhesion-Molecules; Integrins; Interleukin-1; L-Selectin; Leukotriene-B4
AN: 93035989
UD: 9301
MEDLINE EXPRESS (R) 1991-1995 98 of 125
TI: Integrins as a primary signal transduction molecule regulating monocyte immediate-early gene induction.
AU: Yurochko-AD; Liu-DY; Eierman-D; Haskill-S
AD: University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill 27599-7295.
SO: Proc-Natl-Acad-Sci-U-S-A. 1992 Oct 1; 89(19): 9034-8
ISSN: 0027-8424
PY: 1992
LA: ENGLISH
CP: UNITED-STATES
AB: Integrins are cell surface receptors found on monocytes that facilitate adhesion to both cellular and extracellular substrates. These integrins are thought to be involved in the selective gene induction observed after monocyte adhesion to various extracellular matrices. To investigate this hypothesis, we stimulated monocytes with monoclonal antibodies to different integrin receptors to specifically mimic the integrin receptor-ligand interactions. Engagement of the common beta chain of the beta 1 subfamily of integrins resulted in expression of the inflammatory mediator genes, interleukin 1 beta, interleukin 1 receptor antagonist, and monocyte adherence-derived inflammatory gene 6 (MAD-6), whereas engagement of the common beta chain of the beta 2 family did not. Furthermore, to characterize integrin-mediated gene induction, we examined the ability of antibodies to the alpha chain of integrin receptors to regulate gene expression. Engagement of the very late antigen 4 (VLA-4) receptor resulted in induction of all the mediator genes. Receptor crosslinking was required because individual Fab fragments were unable to stimulate gene induction whereas the divalent F(ab')2 fragment and the whole IgG molecule could. Interleukin 1 beta secretion was dependent on the anti-integrin antibody used. Some antibodies required a second signal and, for others, direct engagement was sufficient for protein production. In conclusion, engagement of integrin receptors regulated the production of both inflammatory mediator mRNA and protein. These results suggest that integrin-dependent recognition and adherence may provide the key signals for initiation of the inflammatory response during monocyte diapedesis.
MESH: Antibodies,-Monoclonal; Blotting,-Northern; Gene-Expression; Gene-Expression-Regulation-immunology; Interleukin-1-biosynthesis; RNA-genetics; RNA-isolation-and-purification; RNA,-Messenger-genetics; RNA,-Messenger-isolation-and-purification
MESH: *Gene-Expression-Regulation; *Integrins-physiology; *Monocytes-physiology; *Receptors,-Very-Late-Antigen-physiology; *Signal-Transduction
TG: Human; Support,-U.S.-Gov't,-P.H.S.
GS: MAD-6
PT: JOURNAL-ARTICLE
CN: 1R01A126774; 5T32CA09156CANCI
RN: 0; 0; 0; 0; 0; 63231-63-0
NM: Antibodies,-Monoclonal; Integrins; Interleukin-1; Receptors,-Very-Late-Antigen; RNA,-Messenger; RNA
AN: 93028399
UD: 9301
MEDLINE EXPRESS (R) 1991-1995 99 of 125
TI: Modulation of integrin expression during mast cell differentiation.
AU: Ducharme-LA; Weis-JH
AD: Department of Pathology, University of Utah, School of Medicine, Salt Lake City 84132.
SO: Eur-J-Immunol. 1992 Oct; 22(10): 2603-7
ISSN: 0014-2980
PY: 1992
LA: ENGLISH
CP: GERMANY
AB: Previously we have reported that rodent mast cells synthesize the mRNA encoding the alpha and beta integrin chains (alpha 4, beta 1 and beta 7) of the lymphocyte Peyer's patch adhesion molecule (LPAM)-1 and LPAM-2 lymphocyte homing receptors, and that they possess an alpha 4-containing integrin complex on their cell surface. In this report, we have examined the expression of these integrin chain genes by mature connective tissue mast cells (CTMC) and by bone marrow-derived mast cells (BMMC) differentiated from bone marrow precursor cells in the presence of interleukin (IL)-3 and/or the c-kit ligand (also known as mast cell growth factor and stem cell growth factor). High levels of both the beta 7 and beta 1 transcripts were present in mature CTMC while those encoding the alpha 4 chain were absent. Similarly, when BMMC were grown in IL-3 for 28 days and analyzed for integrin chain transcripts, those specific for the alpha 4 chain were also diminished compared to beta 7 and beta 1 transcripts. To compare the expression of these integrin genes during mucosal mast cell and CTMC development, BMMC were derived in the presence of IL-3 alone, c-kit alone, or IL-3/c-kit together. These experiments indicated that c-kit inhibited the transcription of the beta 7 and Fc epsilon RI genes while enhancing alpha 4 transcript levels. The enhancement of alpha 4 levels, however, was abrogated with the addition of IL-3. Similarly, the c-kit-induced depression of beta 7 and Fc epsilon RI transcript levels was overcome by the addition of IL-3. These data suggest that the integrin complexes synthesized by the mast cells may differ depending upon their path of differentiation and that another alpha chain integrin may be synthesized to complex with the beta 7 and/or beta 1 chains.
MESH: Base-Sequence; Cell-Differentiation-drug-effects; Interleukin-3-pharmacology; Mast-Cells-cytology; Mice-; Molecular-Sequence-Data; Proto-Oncogene-Proteins-pharmacology
MESH: *Gene-Expression; *Integrins-genetics; *Mast-Cells-metabolism
TG: Animal; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: AI24158AINIAID; CA42014CANCI
RN: 0; 0; 0; 0
NM: Integrins; Interleukin-3; Proto-Oncogene-Proteins-c-kit; Proto-Oncogene-Proteins
AN: 93011456
UD: 9301
MEDLINE EXPRESS (R) 1991-1995 100 of 125
TI: Vascular cell adhesion molecule-1 expressed by bone marrow stromal cells mediates the binding of hematopoietic progenitor cells.
AU: Simmons-PJ; Masinovsky-B; Longenecker-BM; Berenson-R; Torok-Storb-B; Gallatin-WM
AD: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA.
SO: Blood. 1992 Jul 15; 80(2): 388-95
ISSN: 0006-4971
PY: 1992
LA: ENGLISH
CP: UNITED-STATES
AB: Human bone marrow-derived CD34+ cells were analyzed for the expression of the beta 1-family of integrin adhesion molecules. Integrin alpha 4 beta 1 was consistently expressed by greater than 90% of CD34+ cells, including essentially all assayable granulocyte-macrophage colony-forming cells (CFU-GM) and erythroid bursts (BFU-E) as shown by fluorescence-activated cell sorting studies. Adhesion of highly enriched CD34+ cells to cultured allogeneic marrow stromal cells was largely inhibited both by monoclonal antibody to alpha 4 beta 1 and to vascular cell adhesion molecule-1 (VCAM-1), a ligand for alpha 4 beta 1. VCAM-1 was found to be expressed by bone marrow stromal elements in vitro both constitutively at low level and at high levels after treatment with cytokines. Induction of VCAM-1 was cytokine- and time-dependent with maximum levels being obtained after 4 hours of exposure to a combination of interleukin-4 and tumor necrosis factor-alpha. Cytokine-induced stromal cells bound threefold higher numbers of CFU-GM and BFU-E, this increase being abrogated by anti-alpha 4 beta 1 and anti-VCAM-1 antibodies. In addition, the adhesion to stroma of more immature progenitors, the long-term culture initiating cells, also occurred through an alpha 4 beta 1/VCAM-1-dependent mechanism. These studies identify an adhesion mechanism of potential importance in the localization of primitive progenitors within the hematopoietic microenvironment.
MESH: Antibodies,-Monoclonal; Bone-Marrow-cytology; Cell-Adhesion-Molecules-immunology; Cells,-Cultured; Hematopoietic-Stem-Cells-cytology; Integrins-analysis; Kinetics-; Time-Factors
MESH: *Antigens,-CD-analysis; *Bone-Marrow-physiology; *Cell-Adhesion; *Cell-Adhesion-Molecules-physiology; *Hematopoietic-Stem-Cells-physiology
TG: Human; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: DK34431DKNIDDK; CA18221CANCI; HL36444HLNHLBI
RN: 0; 0; 0; 0; 0; 0
NM: Antibodies,-Monoclonal; Antigens,-CD; Antigens,-CD34; Cell-Adhesion-Molecules; Integrins; Vascular-Cell-Adhesion-Molecule-1
AN: 92329932
UD: 9210
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 101 of 125
TI: Distribution of surface-membrane molecules on bone marrow and cord blood CD34+ hematopoietic cells.
AU: Saeland-S; Duvert-V; Caux-C; Pandrau-D; Favre-C; Valle-A; Durand-I; Charbord-P; de-Vries-J; Banchereau-J
AD: Schering-Plough Laboratory for Immunological Research, Dardilly, France.
SO: Exp-Hematol. 1992 Jan; 20(1): 24-33
ISSN: 0301-472X
PY: 1992
LA: ENGLISH
CP: UNITED-STATES
AB: We have investigated the distribution of membrane molecules on CD34+ hematopoietic cells isolated from human bone marrow (BM) and cord blood (CB). A distinct CD10+ population was present in BM, but it was not detected in CB. Most CD34+ CD10+ cells in BM were B-cell precursors (BCP), because they expressed CD19. However, CD40 and CD37 were found on the majority of CD34+ cells from either BM or CB, demonstrating that these antigens are not restricted to B-lineage CD34+ cells. CD40 and CD37 were lost during culture of CD34+ cells in the presence of interleukin 3 (IL-3), indicating transient expression early in myeloid development. CD13 antigen was detected on virtually all CD34+ cells from BM and CB. Accordingly, CD13 was present on CD34+ CD10+ cells, demonstrating that this structure is not restricted to myeloid CD34+ cells. In contrast, myeloid CD33 antigen was not detected on CD34+ CD10+ cells. Expression levels of CD13 and of CD33 were heterogeneous in BM, reflecting diversity within the resident CD34+ population. CD25 and CD71 were found on a proportion of CD34+ cells from either BM or CB and maintained during culture in IL-3, consistent with a distribution on activated cells. Finally, a variety of adhesion receptors were present on CD34+ cells. These included the alpha 4 beta 1 (VLA-4), alpha 5 beta 1 (VLA-5), and alpha L beta 2 (LFA-1) integrins, as well as ICAM-1, LFA-3, H-CAM, and LAM-1. Expression of adhesion receptors was remarkably similar in BM and CB, and it followed an all-or-nothing pattern that failed to delineate CD34+ subsets. Taken together, our data show that although CD34+ cells from BM constitute a more heterogeneous population, resident and circulating CD34+ cells largely display the same cell-surface molecules.
MESH: Antigens,-Differentiation,-B-Lymphocyte-analysis; Antigens,-Differentiation,-Myelomonocytic-analysis; Bone-Marrow-ultrastructure; Cell-Adhesion-Molecules-analysis; Cells,-Cultured; Flow-Cytometry; Hematopoietic-Stem-Cells-ultrastructure; Integrins-analysis; Interleukin-3-pharmacology; Receptors,-Interleukin-2-analysis; Receptors,-Very-Late-Antigen-analysis
MESH: *Antigens,-CD-analysis; *Antigens,-Surface-analysis; *Bone-Marrow-chemistry; *Bone-Marrow-cytology; *Fetal-Blood-chemistry; *Fetal-Blood-cytology; *Hematopoietic-Stem-Cells-chemistry; *Hematopoietic-Stem-Cells-immunology; *Membrane-Proteins-analysis
TG: Human
PT: JOURNAL-ARTICLE
RN: EC 3.4.11.2; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 126547-89-5
NM: Antigens,-CD13; Antigens,-CD; Antigens,-CD19; Antigens,-CD34; Antigens,-CD40; Antigens,-Differentiation,-B-Lymphocyte; Antigens,-Differentiation,-Myelomonocytic; Antigens,-Surface; Cell-Adhesion-Molecules; CD33-antigen; CD71-antigen; Integrins; Interleukin-3; Membrane-Proteins; Receptors,-Interleukin-2; Receptors,-Very-Late-Antigen; Intercellular-Adhesion-Molecule-1
AN: 92249491
UD: 9208
MEDLINE EXPRESS (R) 1991-1995 102 of 125
TI: Lymphocyte activation and regulation of three adhesion molecules with supposed function in homing: LECAM-1 (MEL-14 antigen), LPAM-1/2 (alpha 4-integrin) and CD44 (Pgp-1).
AU: Buhrer-C; Berlin-C; Jablonski-Westrich-D; Holzmann-B; Thiele-HG; Hamann-A
AD: Abt. f. Immunologie, Universitatskrankenhaus Eppendorf, Hamburg, Germany.
SO: Scand-J-Immunol. 1992 Jan; 35(1): 107-20
ISSN: 0300-9475
PY: 1992
LA: ENGLISH
CP: ENGLAND
AB: Directed migration of lymphocytes from blood into lymph nodes and gut-associated lymphatic tissue, also referred to as homing, is subject to change following activation. Lymphocyte migration into lymphoid organs in vivo and binding to high endothelial venules in vitro is largely suppressed after short-term stimulation with phorbol esters. The observed functional alterations were correlated with changes in the expression of three putative homing receptors, LECAM-1 (MEL-14 antigen), LPAM-1/2 (alpha 4-integrin) and the murine CD44 (Pgp-1, H-CAM, Hermes-antigen equivalent) upon different modes of cellular activation. Expression of LECAM-1 (gp90 MEL-14), a lymphocyte adhesion molecule implicated in targeting extravasation into lymph nodes, was found to be lost almost completely within minutes after protein kinase C activation. LECAM-1 re-expression occurred within less than 24 h. Rapid loss of LECAM-1 was also observed after calcium ionophores whereas anti-CD3 or concanavalin A elicited a gradual and heterogeneous loss of LECAM-1 becoming detectable after several hours only. A number of cytokines tested were not able to induce alterations in LECAM-1 expression. In contrast, expression of LPAM-1/2 (alpha 4-integrin) and CD44 (Pgp-1, H-CAM), two adhesion molecules supposed to direct extravasation into Peyer's patches, remained stable for hours after every stimulus tested; CD44 expression gradually increased 24 h after mitogenic activation, whereas a small reduction only was observed for the expression of the alpha 4-chain under certain conditions. Thus, reduced extravasation of lymphocytes into Peyer's patches after activation is not due to a decline in the surface density of LPAM-1/2 alpha-chain or CD44 whereas alterations in migration into lymph nodes parallel the expression of LECAM-1.
MESH: Calcimycin-pharmacology; Cell-Adhesion-Molecules-drug-effects; Cell-Movement-immunology; Concanavalin-A-pharmacology; Down-Regulation-Physiology-physiology; Endothelium,-Vascular-ultrastructure; Integrins-immunology; Interleukin-8-pharmacology; Mice-; Mice,-Inbred-BALB-C; Receptors,-Lymphocyte-Homing-drug-effects; Receptors,-Lymphocyte-Homing-immunology; Tetradecanoylphorbol-Acetate-pharmacology; Transforming-Growth-Factor-beta-pharmacology
MESH: *Cell-Adhesion-Molecules-immunology; *Lymphocyte-Transformation-physiology; *Receptors,-Lymphocyte-Homing-physiology
TG: Animal; Female; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 11028-71-0; 126880-86-2; 16561-29-8; 52665-69-7
NM: Cell-Adhesion-Molecules; Integrins; Interleukin-8; Receptors,-Lymphocyte-Homing; Transforming-Growth-Factor-beta; Concanavalin-A; L-Selectin; Tetradecanoylphorbol-Acetate; Calcimycin
AN: 92132492
UD: 9205
MEDLINE EXPRESS (R) 1991-1995 103 of 125
TI: Rapid cytokine up-regulation of integrins, complement receptor 1 and HLA-DR on monocytes but not on lymphocytes.
AU: Limb-GA; Hamblin-AS; Wolstencroft-RA; Dumonde-DC
AD: Immunology Research Unit, Rayne Institute, St Thomas' Hospital, London, U.K.
SO: Immunology. 1992 Sep; 77(1): 88-94
ISSN: 0019-2805
PY: 1992
LA: ENGLISH
CP: ENGLAND
AB: Short-term (3 hr) incubation of whole blood with human recombinant cytokines induced rapid changes in the expression of monocyte but not of lymphocyte surface molecules. The percentage of monocytes bearing CD11b molecules was enhanced by tumour necrosis factor-beta (TNF-beta), whilst that of CD11c was increased by both TNF-alpha and TNF-beta. The mean fluorescence intensity (MFI) of monocyte CD11a was enhanced by interleukin-2 (IL-2), TNF-alpha and TNF-beta, and that of CD11b, CD11c and CD18 was increased by IL-2, IL-4, TNF-alpha and TNF-beta. The proportion of monocytes expressing HLA-DR antigens was not modified by the cytokines investigated, but its MFI was increased by IL-2, IL-4, TNF-alpha and TNF-beta. In contrast, the percentage of monocytes bearing complement receptor 1 (CD35) was enhanced by IL-2, TNF-alpha and TNF-beta but the MFI of this molecule was not modified by these cytokines. The highest up-regulation of CD18, HLA-DR and CD35 was observed with 100 U/ml of either IL-2, IL-4, TNF-alpha or TNF-beta. Decreasing the concentration of all four cytokines from 100 to 10 and 1 U/ml diminished the levels of expression of all molecules, with the exception of CD35, which reached its maximum upon incubation with 1 U/ml of TNF-alpha. IL-1 beta, IL-6 or interferon-gamma (IFN-gamma) did not modify the expression of any of the above monocyte surface determinants. Moreover, none of the lymphocyte surface molecules investigated was modified by 3-hr incubation of blood with cytokines. The demonstration that cytokines selectively and rapidly up-regulate integrins, complement receptor 1 and HLA-DR molecules, on monocytes but not on lymphocytes, suggests that similar mechanisms of mononuclear cell activation by cytokines may control the development and duration of the inflammatory process.
MESH: Antigens,-CD-analysis; Cells,-Cultured; Dose-Response-Relationship,-Immunologic; Lymphocytes-immunology; Recombinant-Proteins-immunology
MESH: *Cytokines-immunology; *HLA-DR-Antigens-analysis; *Integrins-analysis; *Monocytes-immunology; *Receptors,-Complement-3b-analysis
TG: Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0; 0
NM: Antigens,-CD; Antigens,-CD11; Antigens,-CD18; Cytokines; HLA-DR-Antigens; Integrins; Receptors,-Complement-3b; Recombinant-Proteins
AN: 93013926
UD: 9301
MEDLINE EXPRESS (R) 1991-1995 104 of 125
TI: Astrocyte cultures from human embryonic brain: characterization and modulation of surface molecules by inflammatory cytokines.
AU: Aloisi-F; Borsellino-G; Samoggia-P; Testa-U; Chelucci-C; Russo-G; Peschle-C; Levi-G
AD: Neurobiology Section, Istituto Superiore di Sanita, Rome, Italy.
SO: J-Neurosci-Res. 1992 Aug; 32(4): 494-506
ISSN: 0360-4012
PY: 1992
LA: ENGLISH
CP: UNITED-STATES
AB: Astrocyte-enriched cultures were established upon passaging of primary cultures from the myelencephalon and mesencephalon of 7-9-week-old human embryos. Immunocytochemical analysis showed that third-fourth passage cultures were composed of a highly enriched population of proliferating, epithelioid cells, up to 90% of which expressed glial fibrillary acidic protein (GFAP); no macrophages and very few fibroblasts (less than 2%) were present. GFAP expression and proliferation declined upon further culturing in serum-containing medium but could be transiently reinduced by growing the cells in a serum-free chemically defined medium. Large numbers of GFAP+ astrocytes were obtained from each embryo and could be stored frozen and recultured. Using flow cytometric analysis, human astrocyte cultures were examined for basal and cytokine [interferon-gamma (IFN-gamma), interleukin-1 beta (IL-1 beta), and tumor necrosis factor-alpha (TNF-alpha)]-induced expression of molecules that may be involved in astrocyte-T-lymphocyte interactions. Cultured human astrocytes spontaneously expressed major histocompatibility complex (MHC) class I antigens and variable levels of MHC class II; MHC class I levels were increased upon IFN-gamma and TNF-alpha treatment, whereas MHC class II antigens were induced on most of the astrocytes by IFN-gamma. Among the molecules involved in antigen-independent interactions between T lymphocytes and target cells, lymphocyte function-associated molecule-3 (LFA-3) was spontaneously expressed by most cultured human astrocytes, whereas intercellular adhesion molecule-1 (ICAM-1) was present at variable levels in non-stimulated astrocytes and was greatly induced by IFN-gamma, TNF-alpha, and IL-1 beta. In this study we also show that the above cytokines upregulate astroglial expression of adhesion molecules of the integrin family (VLA-1, VLA-2, and VLA-6) that may be involved in astrocyte-extracellular matrix interaction and play a role in the astrocyte reactive changes occurring at sites of brain injury and inflammation. The human astrocyte cultures developed here represent a useful in vitro model to further investigate mechanisms involved in bidirectional communication between central glia and cells of the immune system.
MESH: Astrocytes-drug-effects; Astrocytes-immunology; Cell-Adhesion-Molecules-metabolism; Embryo-drug-effects; Embryo-metabolism; Fibronectins-biosynthesis; Fibronectins-immunology; Flow-Cytometry; Immunohistochemistry-; Integrins-immunology; Integrins-metabolism; Lymphocyte-Function-Associated-Antigen-1-immunology; Lymphocyte-Function-Associated-Antigen-1-metabolism; Macrophages-drug-effects; Macrophages-metabolism; Major-Histocompatibility-Complex-drug-effects; Neuroglia-drug-effects; Neuroglia-metabolism; Pregnancy-; Receptors,-Very-Late-Antigen-immunology; Receptors,-Very-Late-Antigen-metabolism
MESH: *Astrocytes-metabolism; *Brain-cytology; *Cytokines-pharmacology; *Inflammation-physiopathology
TG: Female; Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 126547-89-5
NM: Cell-Adhesion-Molecules; Cytokines; Fibronectins; Integrins; Lymphocyte-Function-Associated-Antigen-1; Receptors,-Very-Late-Antigen; Intercellular-Adhesion-Molecule-1
AN: 92407912
UD: 9212
MEDLINE EXPRESS (R) 1991-1995 105 of 125
TI: Migration of recombinant IL-2-activated T and natural killer cells in the intercellular space of human H-2 glioma spheroids in vitro. A study on adhesion molecules involved.
AU: Jaaskelainen-J; Maenpaa-A; Patarroyo-M; Gahmberg-CG; Somersalo-K; Tarkkanen-J; Kallio-M; Timonen-T
AD: Department of Neurosurgery, University of Helsinki, Finland.
SO: J-Immunol. 1992 Jul 1; 149(1): 260-8
ISSN: 0022-1767
PY: 1992
LA: ENGLISH
CP: UNITED-STATES
AB: The migration of rIL-2-activated T and NK cells into the intercellular space of glioma tissue was studied using multicellular spheroids grown from the human H-2 glioblastoma cell line as targets. Lymphocytes of all analyzed subtypes migrated into the spheroids, but CD56+ cells were particularly migratory. Lymphocytes and the H-2 tissue expressed adhesion molecule subunits for the following potential cell-cell or cell-matrix interactions: alpha 3 beta 1 (VLA-3) to fibronectin, laminin, and collagen; alpha 4 beta 1 (VLA-4) and alpha 5 beta 1 (VLA-5) to fibronectin; alpha 6 beta 1 (VLA-6) to laminin; alpha 4 beta 1 to VCAM-1; alpha L beta 2 (Leu-CAMa/LFA-1) to CD54 (ICAM-1); CD44 to fibronectin, collagen, laminin, hyaluronate; CD2 to CD58 (LFA-3); and CD56 (N-CAM) to CD56. In the H-2 tissue, CD54 and VCAM-1 were expressed as a gradient. The expression of CD54 was weak in the peripheral zone and the expression was stronger in the quiescent deeper zone, whereas the distribution of VCAM-1 showed an inversed pattern. The low expression of CD54 was up-regulated along the frontier of migrating lymphocytes. The migration was almost totally prevented by the anti-CD18 (beta 2) mAb IB4 and TS1/18, and also strongly inhibited by the anti-CD54 mAb LB-2. Instead, mAb known to inhibit the binding of beta 1 integrins to fibronectin were not significantly inhibitory. However, a combination of the GPEILDVPST and GRGDS peptides, which compete for the binding of alpha 4 beta 1 and alpha 5 beta 1 to fibronectin and may also affect other adhesion systems, partially prevented migration.
MESH: Amino-Acid-Sequence; Cell-Adhesion-Molecules-metabolism; Cell-Movement; Glioma-pathology; Intercellular-Junctions-ultrastructure; Interleukin-2-pharmacology; Lymphocyte-Transformation; Molecular-Sequence-Data; Organoids-; Receptors,-Very-Late-Antigen-metabolism; Recombinant-Proteins; Tumor-Cells,-Cultured
MESH: *Glioma-immunology; *Integrins-metabolism; *Killer-Cells,-Lymphokine-Activated-cytology; *Killer-Cells,-Natural-cytology; *T-Lymphocytes-cytology
TG: Human; In-Vitro; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 126547-89-5
NM: Cell-Adhesion-Molecules; Integrins; Interleukin-2; Receptors,-Very-Late-Antigen; Recombinant-Proteins; Intercellular-Adhesion-Molecule-1
AN: 92300021
UD: 9209
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 106 of 125
TI: Monocyte chemoattractant protein-1 regulates adhesion molecule expression and cytokine production in human monocytes.
AU: Jiang-Y; Beller-DI; Frendl-G; Graves-DT
AD: Department of Oral Biology, Boston University Medical Center, MA 02118.
SO: J-Immunol. 1992 Apr 15; 148(8): 2423-8
ISSN: 0022-1767
PY: 1992
LA: ENGLISH
CP: UNITED-STATES
AB: Monocytes play a critical role in defending the host against foreign organisms and in regulating the behavior of other cells. Monocytes circulate as nonadherent cells in the blood and migrate as adherent cells through tissues. Adhesion molecules mediate not only cell adhesion, but also migration, phagocytosis, and many other adhesion-dependent functions. Monocyte chemoattractant protein-1 (MCP-1) is thought to be responsible for monocyte recruitment in acute inflammatory conditions and may be an important mediator in chronic inflammation. In this study, immunofluorescence flow cytometry was used to determine whether MCP-1 can regulate the cell surface expression of adhesion molecules, particularly beta-2 and alpha-4 integrins and the leukocyte adhesion molecule-1. We found that MCP-1 induced expression of CD11c (p150,95 alpha-subunit) and CD11b (Mac-1 alpha-subunit), and caused little or no change of CD11a (lymphocyte function-associated Ag-1 alpha-subunit), very late activation Ag-4, or leukocyte adhesion molecule-1. We demonstrated that antibodies to beta-2 and alpha-4 integrins inhibited MCP-1-induced monocyte chemotaxis. We also showed that MCP-1 is capable of inducing IL-1 and IL-6, but not TNF production of monocytes. These results indicate that MCP-1 is not only a chemoattractant but also a novel cytokine with the capacity to regulate several parameters of monocyte function.
MESH: Cells,-Cultured; Chemotaxis,-Leukocyte-drug-effects; Integrins-physiology; Interleukin-1-biosynthesis; Interleukin-6-biosynthesis; Monocytes-physiology; N-Formylmethionine-Leucyl-Phenylalanine-pharmacology; Tumor-Necrosis-Factor-biosynthesis
MESH: *Antigens,-CD-analysis; *Chemotactic-Factors-pharmacology; *Cytokines-biosynthesis; *Monocytes-drug-effects
TG: Human; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: DE07559DENIDR; DE0958DENIDR; DE08569DENIDR
RN: 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 59880-97-6
NM: monocyte-chemotactic-and-activating-factor; Antigens,-CD; Antigens,-CD11; Antigens,-CD18; Chemotactic-Factors; Cytokines; Integrins; Interleukin-1; Interleukin-6; Tumor-Necrosis-Factor; N-Formylmethionine-Leucyl-Phenylalanine
AN: 92218839
UD: 9207
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 107 of 125
TI: Molecular mechanism of blood monocyte adhesion to vascular endothelial cells.
AU: Dosquet-C; Weill-D; Wautier-JL
AD: UFR Lariboisiere, Saint-Louis, Hopital Lariboisiere, Paris, France.
SO: Nouv-Rev-Fr-Hematol. 1992; 34 Suppl: S55-9
PY: 1992
LA: ENGLISH
CP: GERMANY
AB: The blood monocytes adhere to endothelial cells unstimulated and after stimulation by interleukin-1, tumor necrosis factor or other mediators. This process is mediated through specific molecules on both endothelial cells and monocytes. Using specific monoclonal antibodies and molecular cloning several families of molecules involved in leukocyte endothelial cell interaction have been defined. Leukocyte adhesion molecules include the three beta 2 integrins (CD11/CD18 molecules), VLA-4 and the L-Selectin. E-Selectin (ELAM-1), P-Selectin (GMP-140) and receptors of the immunoglobulin superfamily (ICAM-1, ICAM-2 and VCAM-1) are expressed on endothelial cells in basal conditions and after activation. It has been shown that these adhesive molecules are involved in blood monocyte adhesion to endothelial cells. Monocytes from patients with diabetes mellitus had an increased adhesion to endothelial cells in culture. As estimated by flow cytometry CD11b/CD18 expression on diabetic monocytes was increased. Pentoxifylline reduced CD11b/CD18 expression on normal and diabetic monocytes. This effect was associated to a decrease in monocyte adhesion to endothelial cells.
MESH: Cell-Adhesion-drug-effects; Cell-Adhesion-physiology; Cell-Adhesion-Molecules-physiology; Diabetes-Mellitus,-Insulin-Dependent-pathology; Endothelium,-Vascular-cytology; Integrins-physiology; Monocytes-cytology; Monocytes-drug-effects; Pentoxifylline-pharmacology; Pentoxifylline-therapeutic-use; Peripheral-Vascular-Diseases-drug-therapy; Peripheral-Vascular-Diseases-pathology
MESH: *Endothelium,-Vascular-physiology; *Monocytes-physiology
TG: Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL
RN: 0; 0; 6493-05-6
NM: Cell-Adhesion-Molecules; Integrins; Pentoxifylline
AN: 94051540
UD: 9402
MEDLINE EXPRESS (R) 1991-1995 108 of 125
TI: Neutrophil activation and the effects of interleukin-8/neutrophil-activating peptide 1 (IL-8/NAP-1).
AU: Baggiolini-M; Imboden-P; Detmers-P
AD: Theodor Kocher Institute, University of Bern, Switzerland.
SO: Cytokines. 1992; 4: 1-17
ISSN: 1013-9982
PY: 1992
LA: ENGLISH
CP: SWITZERLAND
MESH: Exocytosis-; G-Proteins-metabolism; Integrins-metabolism; Neutrophils-drug-effects; NADH,-NADPH-Oxidoreductases-blood; Organelles-drug-effects; Organelles-physiology; Signal-Transduction-drug-effects; Superoxides-blood; Up-Regulation-Physiology-drug-effects
MESH: *Interleukin-8-pharmacology; *Neutrophils-physiology
TG: Animal; Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL
RN: EC 1.6.; EC 1.6.-; 0; 0; 0; 11062-77-4
NM: NADH,-NADPH-Oxidoreductases; NADPH-oxidase; G-Proteins; Integrins; Interleukin-8; Superoxides
AN: 93113275
UD: 9304
MEDLINE EXPRESS (R) 1991-1995 109 of 125
TI: Leukocyte adhesion to vascular endothelium.
AU: Ley-K
AD: Department of Physiology, Freie Universitaet Berlin, Germany.
SO: J-Reconstr-Microsurg. 1992 Nov; 8(6): 495-503
ISSN: 0743-684X
PY: 1992
LA: ENGLISH
CP: UNITED-STATES
AB: Leukocyte adhesion and emigration are controlled by soluble mediators and effected by various adhesion molecules. Currently, three major families of adhesion receptors are known to contribute to this process: integrins, vascular selectins, and immunoglobulin-like receptors. These adhesion systems are not additive and mutually replaceable, but appear to constitute a cascade of events. Leukocyte margination is followed by rolling, firm adhesion, emigration, and migration in the interstitial space. In addition, biomechanical parameters like leukocyte deformability and shear stress exerted by the flowing blood modulate the efficacy of adhesive interaction. This article briefly reviews the molecular nature, biologic regulation, and physiologic function of pertinent adhesion receptors.
MESH: Acute-Disease; Integrins-physiology; Interleukins-physiology
MESH: *Cell-Adhesion-immunology; *Endothelium,-Vascular-physiology; *Inflammation-immunology; *Leukocytes-immunology
TG: Animal; Human
PT: JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL
RN: 0; 0
NM: Integrins; Interleukins
AN: 93085645
UD: 9303
MEDLINE EXPRESS (R) 1991-1995 110 of 125
TI: Regulation of integrin gene expression by substrate adherence.
AU: Chen-D; Magnuson-V; Hill-S; Arnaud-C; Steffensen-B; Klebe-RJ
AD: Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio 78284.
SO: J-Biol-Chem. 1992 Nov 25; 267(33): 23502-6
ISSN: 0021-9258
PY: 1992
LA: ENGLISH
CP: UNITED-STATES
AB: Under substrate adherent conditions, integrin gene expression can be regulated by transforming growth factor-beta, interleukin-1 beta, and prostaglandins. This report demonstrates a new mechanism that can differentially control the expression of several integrins. When MG-63 osteosarcoma cells are maintained in suspension, up-regulation of several integrin alpha-subunits takes place. Within as little as 4 h, the mRNA levels for both the alpha 2- and alpha 4-subunits are increased 4- and 6-fold, respectively. It was found that mRNA levels for the alpha 2-, alpha 4-, and alpha v-subunits were markedly increased in several differentiated cell lines under nonadherent conditions; however, cells that did not express a given integrin under substrate adherent conditions also did not express this integrin when maintained in suspension. The alpha 5-subunit did not upregulate during suspension growth. By immunocytochemistry, changes in integrin mRNA levels were confirmed at the protein level. Both cytochalasin B and a phorbol ester were found to induce the expression of the alpha 2-subunit, but not the alpha 4- and alpha 5-subunits, in a dose-dependent fashion. Many investigators have documented changes in gene expression that result from changes in "cell shape." These phenomena may result from up-regulation of integrin gene expression induced by the lack of substrate adherence.
MESH: Base-Sequence; Cell-Division; Cell-Line; Cytochalasin-B-pharmacology; Gene-Expression-Regulation-drug-effects; Gene-Expression-Regulation,-Neoplastic-drug-effects; Kinetics-; Macromolecular-Systems; Molecular-Sequence-Data; Oligodeoxyribonucleotides-; Polymerase-Chain-Reaction-methods; RNA,-Messenger-genetics; RNA,-Messenger-metabolism; Tetradecanoylphorbol-Acetate-pharmacology; Tumor-Cells,-Cultured
MESH: *Cell-Adhesion; *Gene-Expression-Regulation; *Gene-Expression-Regulation,-Neoplastic; *Integrins-genetics
TG: Human; Support,-U.S.-Gov't,-Non-P.H.S.; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: DE08144DENIDR
RN: 0; 0; 0; 0; 14930-96-2; 16561-29-8
NM: Integrins; Macromolecular-Systems; Oligodeoxyribonucleotides; RNA,-Messenger; Cytochalasin-B; Tetradecanoylphorbol-Acetate
AN: 93054698
UD: 9302
MEDLINE EXPRESS (R) 1991-1995 111 of 125
TI: Characterization of adhesion molecules on human myeloma cell lines.
AU: Uchiyama-H; Barut-BA; Chauhan-D; Cannistra-SA; Anderson-KC
AD: Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115.
SO: Blood. 1992 Nov 1; 80(9): 2306-14
ISSN: 0006-4971
PY: 1992
LA: ENGLISH
CP: UNITED-STATES
AB: In multiple myeloma, malignant plasma cells are localized in marrow and rarely circulate in peripheral blood. To investigate the role of adhesion proteins in this process, we determined the expression and function of adhesion molecules on cell lines derived from patients with myeloma. The U266, ARH-77, IM-9, and HS-Sultan cell lines strongly expressed beta 1 and alpha 4 integrins (89% to 98% positive), confirming that VLA-4 is the principal integrin on these cell lines. The U266 and IM-9 cell lines also expressed alpha 3 integrin on 15% to 20% cells. In contrast, all lines lacked cell surface alpha 2, alpha 5, and alpha 6 integrin expression (< 5% positive). These cell lines adhered to fibronectin (20% to 40% specific binding), without significant binding to either collagen or laminin. Adhesion of these cell lines to fibronectin was partially blocked with either anti-beta 1 integrin monoclonal antibody (MoAb) (75% inhibition), anti-alpha 4 integrin MoAb (75% inhibition), or RGD peptide (50% inhibition), but was unaffected by anti-alpha v beta 3 or anti-alpha IIb beta 3 MoAbs. Moreover, the combination of anti-beta 1 plus RGD peptide or anti-alpha 4 plus RGD peptide inhibited binding to fibronectin by 80% and 95%, respectively. Finally, pretreatment and coculture of the IM-9 cell line with interleukin-6 (IL-6) resulted in a 52% decrease in specific binding to fibronectin (30% +/- 6% to 15% +/- 6%; P = .001), associated with a decrease in the number of cells expressing VLA-4 and a decrease in intensity of VLA-4 expression. These data suggest that myeloma cells adhere to fibronectin through VLA-4 as well as through RGD-dependent mechanisms, and that this binding can be downregulated by IL-6. Future studies of binding of both myeloma cell lines and freshly isolated tumor cells to extracellular matrix proteins and to marrow stroma may enhance our understanding of localization and trafficking of cells within the bone marrow microenvironment.
MESH: Collagen-metabolism; Fibronectins-metabolism; Laminin-metabolism; Multiple-Myeloma; Ovarian-Neoplasms; Tumor-Cells,-Cultured
MESH: *Antigens,-CD-analysis; *Cell-Adhesion; *Cell-Adhesion-Molecules-analysis; *Extracellular-Matrix-Proteins-metabolism; *Integrins-analysis
TG: Comparative-Study; Female; Human; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: CA50947CANCI
RN: 0; 0; 0; 0; 0; 0; 9007-34-5
NM: Antigens,-CD; Cell-Adhesion-Molecules; Extracellular-Matrix-Proteins; Fibronectins; Integrins; Laminin; Collagen
AN: 93043346
UD: 9302
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 112 of 125
TI: Interactions between interleukin-2-activated lymphocytes and vascular endothelium: binding to and migration across specialized and non-specialized endothelia.
AU: Pankonin-G; Reipert-B; Ager-A
AD: Central Institute for Cancer Research, Berlin-Buch, Germany.
SO: Immunology. 1992 Sep; 77(1): 51-60
ISSN: 0019-2805
PY: 1992
LA: ENGLISH
CP: ENGLAND
AB: A prerequisite for the successful immunotherapy of solid tumours with interleukin-2 (IL-2)-activated lymphocytes is their ability to home to the tumour tissue. Lymphocyte homing is a complex process which is known to involve at least two independently regulated events: adhesion to the luminal surface of vascular endothelium and the subsequent transendothelial migration of lymphocytes. In this study we have used an in vitro model of lymphocyte homing which employs specialized high endothelium to ask whether IL-2-activated lymphocytes are able to migrate across vascular endothelium in order to leave the blood vessel. Both the adhesion of IL-2-activated cells and their migration across monolayers of cultured high endothelial cells (HEC) were increased in comparison with non-activated lymphocytes. The adhesion of IL-2-activated lymphocytes was mediated by lymphocyte function-associated antigen-1 (LFA-1) and a very late activation antigen-4 (VLA-4)-related pathway. LFA-1-dependent adhesion was mediated by ligands on HEC other than the intercellular adhesion molecule-1 (ICAM-1) and the VLA-4-related pathway was mediated by ligands other than the CS1 domain of fibronectin. HEC-adherent lymphocytes were enriched in natural killer (NK) cells and CD8+ T cells which are known to be the tumour-cytotoxic cells in IL-2-activated lymphocytes. However, there was no evidence of cytotoxicity towards the endothelial layer using a syngeneic model. The interaction of IL-2-activated lymphocytes and endothelial cells was not specific for high endothelium since equal numbers of activated lymphocytes bound to and migrated across aortic endothelium. The inability of IL-2-activated lymphocytes to discriminate between high endothelium and non-specialized 'flat' endothelium could be responsible for the widespread dissemination of the cells throughout the body following their adoptive transfer and the unwanted side-effects at non-involved sites.
MESH: Cell-Adhesion-immunology; Cell-Movement-immunology; Integrins-analysis; Interleukin-2-immunology; Lymphocyte-Function-Associated-Antigen-1-analysis; Lymphocyte-Subsets-immunology; Rats-; Rats,-Inbred-Strains
MESH: *Endothelium,-Vascular-immunology; *Killer-Cells,-Lymphokine-Activated-physiology; *Lymphocytes,-Tumor-Infiltrating-physiology
TG: Animal; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0
NM: integrin-alpha4beta1; Integrins; Interleukin-2; Lymphocyte-Function-Associated-Antigen-1
AN: 93013920
UD: 9301
MEDLINE EXPRESS (R) 1991-1995 113 of 125
TI: T lymphocytes in human atherosclerotic plaques are memory cells expressing CD45RO and the integrin VLA-1.
AU: Stemme-S; Holm-J; Hansson-GK
AD: Department of Clinical Chemistry, Gothenburg University, Sweden.
SO: Arterioscler-Thromb. 1992 Feb; 12(2): 206-11
ISSN: 1049-8834
PY: 1992
LA: ENGLISH
CP: UNITED-STATES
AB: The cellular composition of human atherosclerotic plaques has been analyzed in several immunohistochemical studies in recent years. These studies have shown that the main cell types of the plaque are macrophages, smooth muscle cells, and T lymphocytes. To further characterize the T-lymphocyte population in atherosclerotic plaques, human plaque tissue was digested enzymatically and the released cells were labeled with fluorescent antibodies and analyzed by flow cytometry. Fifteen patients undergoing carotid endarterectomy were studied. Sixty-four percent of plaque T cells expressed the low-molecular-weight form (CD45RO) of the leukocyte common antigen (CD45). Many of these cells expressed the integrin very late activation antigen-1 (VLA-1), which suggests that they are in a state of late activation. In contrast, only 1% of peripheral blood T cells from the same patients expressed VLA-1. Other markers of T cell activation, such as Ta1 (CD26) and HLA-DR, were also increased on plaque T cells. The interleukin-2 receptor (CD25), which is transiently expressed after activation, was present on only a small proportion of the cells. Taken together, this analysis of plaque lymphocytes shows that the majority of plaque T cells are memory cells, many of which are in a state of late or chronic activation. This T-cell phenotype may be the result of a preferential recruitment and/or retention of activated peripheral blood T cells or local antigenic stimulation of resting T cells.
MESH: Aged-; Atherosclerosis-pathology; Lymphocyte-Transformation; Middle-Age; Phenotype-; T-Lymphocytes-physiology
MESH: *Antigens-analysis; *Antigens,-CD-analysis; *Atherosclerosis-immunology; *Histocompatibility-Antigens-analysis; *Immunologic-Memory; *Integrins-immunology; *T-Lymphocytes-immunology
TG: Female; Human; Male; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0
NM: Antigens; Antigens,-CD; Antigens,-CD45; Histocompatibility-Antigens; Integrins
AN: 92181912
UD: 9206
MEDLINE EXPRESS (R) 1991-1995 114 of 125
TI: Collagen-induced release of interleukin 1 from human blood mononuclear cells. Potentiation by fibronectin binding to the alpha 5 beta 1 integrin.
AU: Pacifici-R; Basilico-C; Roman-J; Zutter-MM; Santoro-SA; McCracken-R
AD: Division of Endocrinology and Bone Metabolism, Jewish Hospital of St. Louis, Washington University Medical Center, MO 63110.
SO: J-Clin-Invest. 1992 Jan; 89(1): 61-7
ISSN: 0021-9738
PY: 1992
LA: ENGLISH
CP: UNITED-STATES
AB: PBMC express cell surface receptors for extracellular matrix components known as integrins. We have recently shown that ligand binding to one PBMC integrin, the collagen receptor alpha 2 beta 1, stimulates the secretion of interleukin 1 (IL-1). We have now investigated the role of fibronectin (Fn), an adherence protein that has binding sites for both PBMC and collagen, in the generation of the IL-1 response to collagen. In contrast to collagen, Fn did not stimulate IL-1 release but Fn-depleted serum decreased the release of IL-1 induced by collagen. A polyclonal antiserum directed against Fn also decreased the collagen-induced IL-1 secretion. The IL-1 response to collagen from cells incubated in Fn-depleted serum was restored by the addition of either purified Fn or the 120-kD cell-binding fragment of Fn, which contains the cell-binding site but not the collagen-binding domain. Smaller Arg-Gly-Asp (RGD) peptides failed to enhance the PBMC response to collagen but inhibited in a concentration-dependent fashion the potentiating effect Fn. As expected, a MAb against the alpha 2 beta 1 collagen receptor decreased collagen-induced IL-1 release. However collagen-induced IL-1 release was also inhibited by a MAb against the alpha 5 beta 1 Fn receptor. The effect of the two MAbs was not additive, suggesting that the occupancy of both receptors by ligands is required in order for collagen to induce an maximal response from PBMC. The mechanism by which Fn exerts its effect remains unknown.(ABSTRACT TRUNCATED AT 250 WORDS)
MESH: Amino-Acid-Sequence; Antibodies,-Monoclonal-immunology; Binding-Sites-immunology; Fibronectins-immunology; Fibronectins-pharmacology; Integrins-immunology; Leukocytes,-Mononuclear-drug-effects; Lymphocytes-metabolism; Molecular-Sequence-Data; Monocytes-metabolism; Oligopeptides-metabolism; Oligopeptides-pharmacology
MESH: *Collagen-pharmacology; *Fibronectins-metabolism; *Integrins-metabolism; *Interleukin-1-secretion; *Leukocytes,-Mononuclear-metabolism
TG: Human; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: AR39706ARNIAMS
RN: 0; 0; 0; 0; 0; 9007-34-5; 99896-85-2
NM: Antibodies,-Monoclonal; Fibronectins; Integrins; Interleukin-1; Oligopeptides; Collagen; arginyl-glycyl-aspartic-acid
AN: 92105408
UD: 9204
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 115 of 125
TI: Regulation of transendothelial neutrophil migration by endogenous interleukin-8 [published errata appear in Science 1991 Nov 1;254(5032):631 and 1991 Dec 6;254(5037):1435]
AU: Huber-AR; Kunkel-SL; Todd-RF 3d; Weiss-SJ
AD: Department of Internal Medicine, University of Michigan, Ann Arbor 48109.
SO: Science. 1991 Oct 4; 254(5028): 99-102
ISSN: 0036-8075
PY: 1991
LA: ENGLISH
CP: UNITED-STATES
AB: Movement of neutrophils from the bloodstream to inflamed tissue depends on the activation of both the neutrophil and the endothelial cell. Endothelial cells lining the postcapillary venule respond to proinflammatory mediators by expressing adhesion molecules and synthesizing a variety of neutrophil-activating factors. Endothelial cell production of a 77-amino acid variant of interleukin-8 (IL-8) was found to be a requirement for the invasion of neutrophils through a vessel wall model. IL-8 secreted by cytokine- or lipopolysaccharide-stimulated endothelial cells induced the rapid shedding of neutrophil lectin adhesion molecule-1, the up-regulation of leukocyte beta 2 integrins, and the attachment and transmigration of the neutrophils. Thus, endogenous endothelial IL-8 regulates transvenular traffic during acute inflammatory responses.
MESH: Antigens,-CD-metabolism; Blotting,-Northern; Cell-Adhesion-Molecules-metabolism; Cell-Movement; Cells,-Cultured; Chemotaxis,-Leukocyte; Gene-Expression; Integrins-metabolism; Interleukin-1-pharmacology; Interleukin-8-genetics; Lipopolysaccharides-; Tumor-Necrosis-Factor-pharmacology
MESH: *Endothelium,-Vascular-physiology; *Interleukin-8-physiology; *Neutrophils-physiology
TG: Human; In-Vitro; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: HL28024HLNHLBI; CA39064CANCI
RN: 0; 0; 0; 0; 0; 0; 0; 0; 0; 126547-89-5
NM: Antigens,-CD; Antigens,-CD18; Cell-Adhesion-Molecules; E-Selectin; Integrins; Interleukin-1; Interleukin-8; Lipopolysaccharides; Tumor-Necrosis-Factor; Intercellular-Adhesion-Molecule-1
AN: 92022554
UD: 9201
MEDLINE EXPRESS (R) 1991-1995 116 of 125
TI: Endothelial-leukocyte adhesion molecule 1 stimulates the adhesive activity of leukocyte integrin CR3 (CD11b/CD18, Mac-1, alpha m beta 2) on human neutrophils.
AU: Lo-SK; Lee-S; Ramos-RA; Lobb-R; Rosa-M; Chi-Rosso-G; Wright-SD
AD: Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, New York 10021.
SO: J-Exp-Med. 1991 Jun 1; 173(6): 1493-500
ISSN: 0022-1007
PY: 1991
LA: ENGLISH
CP: UNITED-STATES
AB: Two classes of adhesion molecules have well-defined roles in the attachment of unstimulated polymorphonuclear leukocytes (PMN) to cytokine-treated endothelial cells. Endothelial-leukocyte adhesion molecule 1 (ELAM-1) on endothelial cells interacts with specific carbohydrate residues on the PMN, and the leukocyte integrins (CD18 antigens) on PMN interact with intracellular adhesion molecule 1 and other structures on endothelium. Here we show that these two classes of molecules can act sequentially in an "adhesion cascade". Interaction of PMN with ELAM-1-bearing endothelial cells causes PMN to express enhanced adhesive activity of the integrin CR3 (CD11b/CD18). Expression of ELAM-1 on the cytokine-treated endothelium appears both necessary and sufficient for the stimulation of CR3 activity since blockade of ELAM-1 with mAbs prevents the activation of CR3 by cytokine-treated endothelium, and immobilized recombinant ELAM-1 activates CR3. The ability to activate CR3 is shared by chemattractants, suggesting that ELAM-1 may serve as a "tethered chemattractant." This hypothesis is strengthened by the observation that recombinant soluble ELAM-1 directs movement of PMN in chemotaxis chambers. These results suggest a mechanism by which multiple adhesive molecules may function together in diapedesis. ELAM-1 serves both as an adhesin and as a trigger that recruits the participation of additional adhesion molecules. Our results also suggest that ligands for adhesion molecules may also be "receptors" capable of generating intracellular signals.
MESH: Antibodies,-Monoclonal; Chemotactic-Factors-physiology; Chemotaxis,-Leukocyte; Endothelium,-Vascular-cytology; Integrins-physiology; Interleukin-1-pharmacology; Interleukin-8-pharmacology; Lipopolysaccharides-pharmacology; Recombinant-Proteins; Tumor-Necrosis-Factor-pharmacology
MESH: *Cell-Adhesion; *Cell-Adhesion-Molecules-physiology; *Macrophage-1-Antigen-physiology; *Neutrophils-cytology
TG: Human; In-Vitro; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: AI22004AINIAID; AI24775AINIAID
RN: 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0
NM: Antibodies,-Monoclonal; Cell-Adhesion-Molecules; Chemotactic-Factors; E-Selectin; Integrins; Interleukin-1; Interleukin-8; Lipopolysaccharides; Macrophage-1-Antigen; Recombinant-Proteins; Tumor-Necrosis-Factor
AN: 91237295
UD: 9108
MEDLINE EXPRESS (R) 1991-1995 117 of 125
TI: Selective up-regulation of human granulocyte integrins and complement receptor 1 by cytokines.
AU: Limb-GA; Hamblin-AS; Wolstencroft-RA; Dumonde-DC
AD: Immunology Research Unit, Rayne Institute, St Thomas' Hospital, London.
SO: Immunology. 1991 Dec; 74(4): 696-702
ISSN: 0019-2805
PY: 1991
LA: ENGLISH
CP: ENGLAND
AB: The percentage of human granulocytes expressing the integrins CD11b and CD11c as well as complement receptor 1 (CD35) was increased by short-term incubation of whole blood with interleukin-2 (IL-2), interleukin-4 (IL-4) and tumour necrosis factors alpha and beta (TNF-alpha and TNF-beta). The mean fluorescence intensity of granulocyte CD18 was also increased by the above cytokines, whilst that of CD11b was only increased by TNF-alpha. Up-regulation of granulocyte CD18 expression was seen with 1 U/ml of IL-2, TNF-alpha or TNF-beta, in contrast to the effect of IL-4 which was only observed with 100 U/ml. Similarly, enhanced expression of CD35 was induced by 1 U/ml of IL-2 or TNF-alpha but not by concentrations of IL-4 or TNF-beta lower than 100 U/ml. Cytokine effects on the CD11/CD18 complex and CD35 molecules were not modified by cycloheximide, suggesting that their increased expression was not due simply to synthesis de novo. None of the granulocyte surface determinants investigated was altered upon short-term incubation of blood with either IL-1, IL-6 or interferon-gamma (IFN-gamma). The demonstration in vitro that cytokines selectively up-regulate granulocyte integrins and complement receptor 1, suggests that similar mechanisms may be operating during the control of granulocyte-mediated inflammatory processes.
MESH: Antigens,-CD-analysis; Cells,-Cultured; Cycloheximide-immunology; Dose-Response-Relationship,-Immunologic
MESH: *Cytokines-immunology; *Granulocytes-immunology; *Integrins-analysis; *Receptors,-Complement-analysis
TG: Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0; 66-81-9
NM: Antigens,-CD; Antigens,-CD11; Antigens,-CD18; Cytokines; Integrins; Receptors,-Complement-3b; Receptors,-Complement; Cycloheximide
AN: 92147209
UD: 9205
MEDLINE EXPRESS (R) 1991-1995 118 of 125
TI: Role of beta 1 integrins in tumor cell adhesion to cultured human endothelial cells.
AU: Lauri-D; Martin-Padura-I; Biondelli-T; Rossi-G; Bernasconi-S; Giavazzi-R; Passerini-F; Van-Hinsbergh-V; Dejana-E
AD: Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
SO: Lab-Invest. 1991 Nov; 65(5): 525-31
ISSN: 0023-6837
PY: 1991
LA: ENGLISH
CP: UNITED-STATES
AB: We investigated the effects of beta 1 integrins on tumor cell (TC) adhesion to unstimulated and interleukin-1 (IL-1) activated endothelial cells (EC). IL-1 treatment (20 units/ml for 6 hours) of cultured human umbilical vein EC significantly increased adhesion of seven human TC lines of different origin. A goat antiserum raised to purified alpha 5 beta 1 integrin abolished the IL-1 induced increment in adhesion of two osteosarcomas, one melanoma, one lung, and one kidney carcinoma, whereas it did not affect adhesion of two colon carcinoma cell lines. Further studies were performed on MG63 osteosarcoma cells. Adhesion of MG63 osteosarcoma cells to EC was dependent on time of EC treatment with IL-1: it was maximal at 12 hours and declined at 24 hours. alpha 5 beta 1 antiserum blocked IL-1 induced increase in MG63 adhesion at any time of EC treatment. This effect appears to be mainly directed to MG63 integrins since selective incubation of the antiserum with EC, but not with MG63, did not modify TC adhesion. Using a series of antibodies to different alpha and beta chains, we found that only monoclonal antibodies (mAb) to alpha 4, alpha 5, and beta 1 could inhibit MG63 adhesion to IL-1 activated EC, whereas alpha 2, alpha 6, and beta 3 antibodies were ineffective. Antibodies to fibronectin had very little activity on MG63 adhesion to EC matrix and did not significantly affect MG63 adhesion to control or IL-1 treated EC. Antibodies to alpha 4, alpha 5, and beta 1 were only partially effective in inhibiting MG63 adhesion to EC matrix. These data indicate that the capacity of alpha 4 beta 1 and alpha 5 beta 1 integrins to bind fibronectin contributed very little to MG63 adhesion to EC. The importance of beta 1 integrins in promoting a direct interaction between EC and MG63 was further shown by inhibition of rosette formation among these cells in suspension by the alpha 5 beta 1 antiserum. Only a VCAM-1/INCAM110 mAb, but not ELAM-1 or ICAM-1 mAbs, could inhibit MG63 adhesion to IL-1 activated EC. Overall these data indicate that at least two members of the beta 1 integrin subfamily (alpha 4 beta 1 and alpha 5 beta 1) are involved in MG63 adhesion to cytokine treated EC. This integrin function might be important at early stages of TC interaction with the vessel wall.
MESH: Antibodies,-Monoclonal; Cell-Adhesion; Cell-Adhesion-Molecules-physiology; Cells,-Cultured; Cytokines-pharmacology; Extracellular-Matrix-physiology; Integrins-immunology
MESH: *Endothelium,-Vascular-cytology; *Integrins-physiology; *Tumor-Cells,-Cultured-physiology
TG: Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0
NM: Antibodies,-Monoclonal; Cell-Adhesion-Molecules; Cytokines; Integrins
AN: 92092637
UD: 9204
MEDLINE EXPRESS (R) 1991-1995 119 of 125
TI: IL-1 beta and prostaglandins regulate integrin mRNA expression.
AU: Milam-SB; Magnuson-VL; Steffensen-B; Chen-D; Klebe-RJ
AD: Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio 78284.
SO: J-Cell-Physiol. 1991 Nov; 149(2): 173-83
ISSN: 0021-9541
PY: 1991
LA: ENGLISH
CP: UNITED-STATES
AB: The purpose of this study was to examine the effects of IL-1 beta on integrin expression in MG-63 human osteosarcoma cells. Human recombinant IL-1 beta (rIL-1 beta) produced significant increases in both alpha 2- and alpha 5-subunit mRNA levels, as well as a smaller increase in alpha v-subunit mRNA. In contrast, IL-1 beta decreased alpha 4-subunit mRNA levels by approximately 30% relative to untreated controls. These findings suggest that human IL-1 beta differentially regulates expression of integrins. When cultures were treated with both IL-1 beta and the cyclooxygenase inhibitor, indomethacin, the expression of alpha 2-, alpha 5-, and alpha v-subunit mRNA levels were dramatically increased relative to untreated controls; co-treatment with 0.5 mM prostaglandin E2 (PGE2) partially reversed this effect. Indomethacin alone did not affect integrin mRNA levels. Treatment with IL-1 beta or IL-1 beta + indomethacin also induced significant changes in MG-63 morphology (i.e., increased cell elongation) and increased the ability of cells to contract collagen gels. PGE2 reversed the above effects on cell morphology and gel contraction. These findings indicate that (a) IL-1 beta differentially regulates the expression of integrins and (b) that PGE2, which is induced by IL-1 beta, may provide a negative feedback loop which counteracts the stimulatory effect of IL-1 beta on integrin gene expression. It is suggested that products of inflammation may affect cell behavior by differentially regulating the expression of various integrins.
MESH: Actins-genetics; Base-Sequence; Cell-Adhesion-drug-effects; Collagen-chemistry; Dinoprostone-biosynthesis; Fluorescent-Antibody-Technique; Indomethacin-pharmacology; Integrins-biosynthesis; Molecular-Sequence-Data; Recombinant-Proteins-pharmacology; RNA,-Messenger-analysis; Tumor-Cells,-Cultured
MESH: *Dinoprostone-pharmacology; *Gene-Expression-Regulation-drug-effects; *Integrins-genetics; *Interleukin-1-pharmacology; *RNA,-Messenger-genetics
TG: Human; Support,-U.S.-Gov't,-Non-P.H.S.; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: DE08144DENIDR; AG06872AGNIA
RN: 0; 0; 0; 0; 0; 363-24-6; 53-86-1; 9007-34-5
NM: Actins; Integrins; Interleukin-1; Recombinant-Proteins; RNA,-Messenger; Dinoprostone; Indomethacin; Collagen
AN: 92084770
UD: 9203
MEDLINE EXPRESS (R) 1991-1995 120 of 125
TI: A novel beta 4, alpha 6 integrin-associated epithelial cell antigen involved in natural killer cell and antigen-specific cytotoxic T lymphocyte cytotoxicity.
AU: Phillips-JH; McKinney-L; Azuma-M; Spits-H; Lanier-LL
AD: DNAX Research Institute for Molecular and Cellular Biology, Palo Alto, California 94304.
SO: J-Exp-Med. 1991 Dec 1; 174(6): 1571-81
ISSN: 0022-1007
PY: 1991
LA: ENGLISH
CP: UNITED-STATES
AB: Efficient immune responses require interactions between cell adhesion molecules on lymphocytes and counter-receptors on antigen presenting cells or target cells. While target-specific receptors or ligands have not been identified for natural killer (NK) cells, cell adhesion molecules have been implicated in the interaction between NK cell effectors and tumor cell targets. Herein, we describe monoclonal antibodies (mAbs) against a carcinoma cell line that efficiently block the cytolytic activity of interleukin 2-activated NK cell lines and clones. L280 mAb reacts with secretory epithelial cells in normal human tissues, but does not react with hematopoietic cells or other tissue types. Biochemical analysis revealed that L280 mAb immunoprecipitates the beta 4, alpha 6 integrin, as well as a novel 98-kD glycoprotein, and probably reacts with a carbohydrate epitope on these molecules. Involvement of the L280 antigen in cellular immunity is not restricted to NK cell-mediated cytotoxicity. L280 mAb also efficiently inhibits alloantigen-specific cytotoxicity against Colo-205 cells mediated by human histocompatibility leukocyte antigen (HLA)-A2 alloantigen specific alpha beta-TCR+ and gamma delta-TCR+ cytotoxic T lymphocyte (CTL) clones. Additionally, we demonstrate that L280 mAb blocks cytotoxicity mediated by influenza peptide-specific HLA-restricted CTL clones. These data indicate that the antigen recognized by L280 mAb is important in both NK and CTL function, and that an as yet unidentified receptor for this epithelial antigen is present on both NK and T lymphocytes. The restricted expression of L280 antigen indicates that this molecule may be important in immune reactions in epithelial tissues.
MESH: Antibodies,-Monoclonal-immunology; Cell-Line; Epithelium-immunology; HLA-A2-Antigen-immunology; Interleukin-2-pharmacology; Receptors,-Antigen,-T-Cell-physiology
MESH: *Adenocarcinoma-immunology; *Antigens,-Neoplasm-physiology; *Colonic-Neoplasms-immunology; *Cytotoxicity,-Immunologic; *Integrins-physiology; *Killer-Cells,-Natural-immunology; *T-Lymphocytes,-Cytotoxic-immunology
TG: Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0
NM: Antibodies,-Monoclonal; Antigens,-Neoplasm; HLA-A2-Antigen; Integrins; Interleukin-2; Receptors,-Antigen,-T-Cell
AN: 92078868
UD: 9203
MEDLINE EXPRESS (R) 1991-1995 121 of 125
TI: Regulation of integrin-type cell adhesion receptors by cytokines.
AU: Santala-P; Heino-J
AD: Department of Medical Biochemistry, University of Turku, Finland.
SO: J-Biol-Chem. 1991 Dec 5; 266(34): 23505-9
ISSN: 0021-9258
PY: 1991
LA: ENGLISH
CP: UNITED-STATES
AB: Integrin heterodimers which share a common beta 1 subunit are the major cellular receptors for many extracellular matrix proteins. Here, we show that two inflammatory mediators, interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha), can regulate the expression of the alpha 1 beta 1 integrin heterodimer, known to be a laminin and collagen receptor. In human skin fibroblasts 10 units/ml IL-1 beta increase the biosynthesis of the alpha 1 integrin subunit an average of 4.5-fold. Furthermore, IL-1 beta can turn on alpha 1 subunit expression in MG-63 human osteosarcoma cells even in conditions where the untreated MG-63 cells do not express it in detectable amounts. The effect of TNF-alpha on alpha 1 subunit expression is similar. Both IL-1 beta and TNF-alpha increased MG-63 cell adhesion on laminin. The effect of transforming growth factor-beta 1 (TGF-beta 1) on integrin expression in MG-63 cells has been previously described (Heino, J., and Massague, J. (1989) J. Biol. Chem. 264, 21806-21811). TGF-beta 1 decreases the biosynthesis of alpha 3 subunit but increases the production of alpha 2 subunit. IL-1 beta potentiates the effects of TGF-beta 1. Furthermore, in the presence of TGF-beta 1 the increase in the expression of alpha 1 subunit by IL-1 beta is even larger. Thus, IL-1 beta and TGF-beta 1, which usually have antagonistic functions in connective tissue, can regulate integrin expression in a synergistic way.
MESH: Cell-Count; Cells,-Cultured; Dinoprostone-pharmacology; Indomethacin-pharmacology; Interleukin-1-pharmacology; Laminin-metabolism; Transforming-Growth-Factor-beta-pharmacology; Tumor-Cells,-Cultured; Tumor-Necrosis-Factor-pharmacology
MESH: *Cell-Adhesion; *Cytokines-pharmacology; *Integrins-metabolism
TG: Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 363-24-6; 53-86-1
NM: Cytokines; Integrins; Interleukin-1; Laminin; Transforming-Growth-Factor-beta; Tumor-Necrosis-Factor; Dinoprostone; Indomethacin
AN: 92078234
UD: 9203
MEDLINE EXPRESS (R) 1991-1995 122 of 125
TI: Adhesive interactions between fibroblasts and polymorphonuclear neutrophils in vitro.
AU: Shock-A; Laurent-GJ
AD: Department of Thoracic Medicine, National Heart and Lung Institute, University of London, United Kingdom.
SO: Eur-J-Cell-Biol. 1991 Apr; 54(2): 211-6
ISSN: 0171-9335
PY: 1991
LA: ENGLISH
CP: GERMANY
AB: Although the in vivo interaction between polymorphonuclear neutrophils (PMN) and fibroblasts may be important, these pathways have not been well studied. We have investigated the adherence of PMN to monolayers of human fetal lung fibroblasts, using a microtiter plate assay based upon the uptake by cells of the vital stain Rose Bengal. Stimulation with phorbol myristate acetate (PMA) caused a significant increase of adherence over basal levels which was rapid in onset and plateaued at 5 min. Adhesion was dependent on the leucocyte integrin family of glycoproteins, notably on Mac-1, since monoclonal antibodies toward the beta chain (CD18) and alpha chain (CD11b) of Mac-1 almost completely suppressed PMA-induced PMN adhesion (88% and 77% inhibition, respectively). Adhesion was also inhibited by the peptides RGDS and GRGDS (24.2% and 26.6%, respectively using 1 mM peptide). Prestimulation of fibroblasts for longer time periods (5 and 24 h) with interleukin 1 alpha and tumor necrosis factor alpha, but not transforming growth factor beta, also resulted in a significant increase in adhesion of unstimulated PMN (after 24 h preincubation, 10 U/ml IL1 alpha stimulated adhesion by 179% of control, 500 U/ml TNF alpha by 157%). This indicated that there are both PMN- and fibroblast-dependent pathways for PMN adhesion. Components of the extracellular matrix of fibroblasts do not appear to play important roles in the adhesion process since addition of fibronectin and type IV collagen, or of purified antibodies to fibronectin and types I and IV collagen, did not affect PMA-induced PMN adhesion.(ABSTRACT TRUNCATED AT 250 WORDS)
MESH: Amino-Acid-Sequence; Antibodies,-Monoclonal; Cell-Adhesion-drug-effects; Cell-Adhesion-Molecules-physiology; Cells,-Cultured; Fibroblasts-drug-effects; Integrins-physiology; Interleukin-1-pharmacology; Kinetics-; Lung-cytology; Molecular-Sequence-Data; Neuraminidase-metabolism; Neutrophils-drug-effects; Tetradecanoylphorbol-Acetate-pharmacology; Transforming-Growth-Factor-beta-pharmacology; Tumor-Necrosis-Factor-pharmacology
MESH: *Cell-Adhesion-physiology; *Fibroblasts-physiology; *Neutrophils-physiology
TG: Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: EC 3.2.1.18; 0; 0; 0; 0; 0; 0; 16561-29-8
NM: Neuraminidase; Antibodies,-Monoclonal; Cell-Adhesion-Molecules; Integrins; Interleukin-1; Transforming-Growth-Factor-beta; Tumor-Necrosis-Factor; Tetradecanoylphorbol-Acetate
AN: 91348061
UD: 9112
MEDLINE EXPRESS (R) 1990 123 of 125
TI: Human melanoma cells with high susceptibility to cell-mediated lysis can be identified on the basis of ICAM-1 phenotype, VLA profile and invasive ability.
AU: Anichini-A; Mortarini-R; Supino-R; Parmiani-G
AD: Division of Experimental Oncology D, Istituto Nazionale Tumori, Milan, Italy.
SO: Int-J-Cancer. 1990 Sep 15; 46(3): 508-15
ISSN: 0020-7136
PY: 1990
LA: ENGLISH
CP: UNITED-STATES
AB: Marked heterogeneity for susceptibility to lysis by autologous CTL clones and allogeneic IL-2-activated CD3- and CD3+ lymphocytes was found among 19 clones isolated from a human metastatic melanoma (Me665/2). A subset of 5 clones with the highest susceptibility to lysis had increased ICAM-1 antigen expression. Phenotype analysis for the presence of extracellular matrix receptors in the beta 1- and beta 3-integrin families revealed that the tumor clones with the highest susceptibility to lysis were also characterized by frequent expression or increased expression of multiple receptors in the beta 1 family including VLA-1, -2, -3, -4 and -6. The correlation between phenotypic markers and susceptibility to lysis, seen at the clonal level, was confirmed by selection experiments on the uncloned metastasis Me665/2. In fact, the neoplastic population surviving 3 cycles of immunoselection with IL-2-activated lymphocytes exhibited, in comparison to the unselected metastasis: (1) reduced susceptibility to lysis and (2) reduced expression of ICAM-1 and of VLA antigens. In contrast, enhanced susceptibility to lysis and up-regulation of ICAM-1, VLA-1 and VLA-3 antigens were observed on melanoma cells recovered after invading a reconstituted basement membrane. These data indicate that melanoma cells with enhanced susceptibility to cell-mediated lysis can be identified on the basis of phenotypic characteristics (ICAM-1 and VLA antigen profile) and functional features (invasive ability on reconstituted basement membranes).
MESH: Antibodies,-Monoclonal; Cell-Adhesion-Molecules-immunology; Cell-Survival; Clone-Cells; Cytotoxicity,-Immunologic; Flow-Cytometry; Integrins-immunology; Integrins-metabolism; Interleukin-2-pharmacology; Lymphocyte-Transformation; Melanoma-immunology; Neoplasm-Invasiveness-immunology; Phenotype-; T-Lymphocytes,-Cytotoxic-drug-effects; T-Lymphocytes,-Cytotoxic-metabolism; Tumor-Cells,-Cultured
MESH: *Cell-Adhesion-Molecules-metabolism; *Melanoma-metabolism; *Receptors,-Very-Late-Antigen-analysis
TG: Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 126547-89-5
NM: Antibodies,-Monoclonal; Cell-Adhesion-Molecules; Integrins; Receptors,-Very-Late-Antigen; Intercellular-Adhesion-Molecule-1
AN: 90368238
UD: 9012
MEDLINE EXPRESS (R) 1990 124 of 125
TI: Immune and inflammatory processes in cutaneous tissues. Mechanisms and speculations [published erratum appears in J Clin Invest 1991 Feb;87(2):753]
AU: Kupper-TS
AD: Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
SO: J-Clin-Invest. 1990 Dec; 86(6): 1783-9
ISSN: 0021-9738
PY: 1990
LA: ENGLISH
CP: UNITED-STATES
MESH: Antigens,-CD-physiology; Chemotaxis-; Cytokines-physiology; Epidermis-immunology; Epidermis-physiology; Integrins-physiology; Interleukin-1-physiology; Leukocytes-physiology; Skin-immunology; T-Lymphocytes-physiology
MESH: *Cell-Adhesion-Molecules-physiology; *Inflammation-physiopathology; *Skin-physiology
TG: Animal; Human; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL
CN: AI25082AINIAID; AR40124ARNIAMS
RN: 0; 0; 0; 0; 0
NM: Antigens,-CD; Cell-Adhesion-Molecules; Cytokines; Integrins; Interleukin-1
AN: 91072649
UD: 9103
SB: AIM
MEDLINE EXPRESS (R) 1990 125 of 125
TI: IL-5 enhances the in vitro adhesion of human eosinophils, but not neutrophils, in a leucocyte integrin (CD11/18)-dependent manner.
AU: Walsh-GM; Hartnell-A; Wardlaw-AJ; Kurihara-K; Sanderson-CJ; Kay-AB
AD: Department of Allergy & Clinical Immunology, National Heart & Lung Institute, Mill Hill, London, U.K.
SO: Immunology. 1990 Oct; 71(2): 258-65
ISSN: 0019-2805
PY: 1990
LA: ENGLISH
CP: ENGLAND
AB: In an attempt to explain the preferential accumulation of eosinophils at sites of allergic tissue reactions, we have studied the effects of interleukin-5 (IL-5) on the adherence of human eosinophils and neutrophils to plasma-coated glass (PCG) or human microvascular endothelial cells (HMVEC). IL-5 was compared with IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF) and platelet-activating factor (PAF), since all these agents have biological properties associated with eosinophil activation and/or survival in vitro. IL-5, IL-3 and GM-CSF induced a time-dependent increase in adherence of normal density eosinophils to PCG optimal at 60 min, whereas the effect of PAF was greater at 15 min. Similar results were obtained with neutrophils, with the exception that IL-5 had minimal and non-significant effects on this cell type. Unstimulated eosinophils and neutrophils also adhered to PCG or HMVEC, but in low numbers. Preincubation of eosinophils with IL-5, GM-CSF or PAF resulted in dose-dependent increases in the numbers of adherent cells to PCG. IL-3 had a smaller but significant effect on enhanced eosinophil adhesion to PCG, while IL-2 and lyso-PAF were ineffective. Neutrophils gave similar levels of baseline and stimulated adhesion to PCG as eosinophils, IL-5 again had no significant stimulatory effect. IL-5 also increased eosinophil, but not neutrophil, adherence to HMVEC in a concentration-dependent manner. Preincubation with the protein synthesis inhibitor cycloheximide had no effect on IL-5-, GM-CSF- or PAF-stimulated eosinophil adhesion. The contribution of the CD11/18 leucocyte integrins to IL-5- and PAF-induced eosinophil hyperadherence was investigated by inhibition experiments utilizing monoclonal antibodies (mAb). Enhanced adhesion to PCG (by PAF) or HMVEC (by IL-5) was inhibited by (ranked in order of potency) anti-CR3 alpha = common beta-chain greater than LFA-1 alpha. Anti-p150,95 alpha had no measurable effect. Baseline adhesion by unstimulated eosinophils was not significantly influenced by prior incubation with these mAb. Using flow cytometry, IL-5 and IL-3 were found to up-regulate cosinophil but not neutrophil CR3 expression. These findings demonstrate that IL-5 enhances cosinophil, but not neutrophil, adherence reactions, by a mechanism dependent, at least in part, on the CD11/18 family of adhesion glycoproteins.
MESH: Cell-Adhesion-immunology; Cells,-Cultured; Dose-Response-Relationship,-Immunologic; Endothelium,-Vascular-physiology; Glass-; Plasma-physiology; Time-Factors
MESH: *Eosinophils-immunology; *Integrins-immunology; *Interleukin-5-immunology; *Neutrophils-immunology
TG: Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0
NM: Glass; Integrins; Interleukin-5
AN: 91033906
UD: 9102