Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the adhesion of human peripheral blood T lymphocytes to human synovial fibroblasts stimulated with interferon-gamma (IFN gamma), tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta), or combinations of these cytokines. T lymphocytes bound poorly to untreated human synovial fibroblasts. IFN gamma treatment resulted in the largest increase in adhesion, followed by TNF alpha and IL-1 beta. Combinations of IFN gamma + TNF alpha and IFN gamma + IL-1 beta had a synergistic effect on intercellular adhesion molecule 1 (ICAM-1) expression and adhesion. The increase in cellular adhesion induced by cytokines correlated with the up-regulation of the number of cells expressing ICAM-1 and the density of antigen/cell. There was no synergistic effect on leukocyte function-associated antigen 3 (LFA-3) or on HLA class I or class II antigen expression. Adhesion was only partially inhibited by anti-ICAM-1, anti-LFA-1, or anti-CD18. These findings suggest the existence of ICAM-1--independent and CD11/CD18-independent adhesion mechanisms. Anti-LFA-3 was completely ineffective as an inhibitor of adhesion. There was no additive or synergistic advantage of using combinations of antibodies to increase the level of inhibition, i.e., anti--ICAM-1 + anti-LFA-3, anti-ICAM-1 + anti-CD18, or anti-ICAM-1 + anti-LFA-1 (CD11a). Our data indicate that proinflammatory cytokines may play a prominent role in the formation and exacerbation of synovial hyperplasia, by regulating the recruitment and retention of T lymphocytes via the up-regulation of adhesion molecules on synovial fibroblasts.
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PMID:T lymphocyte adhesion to human synovial fibroblasts. Role of cytokines and the interaction between intercellular adhesion molecule 1 and CD11a/CD18. 168 12

We examined the actions of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) on neutrophil and monocyte (phagocyte) adhesion to human mesangial cell monolayers (HMC) and assessed the role of phagocyte CD11/CD18 integrin adhesion molecules and HMC intercellular adhesion molecule-1 (ICAM-1) in this process, using subunit specific monoclonal antibodies (MAb). TNF, but not IL-1, provoked rapid (onset less than 1 min) neutrophil and monocyte adhesion to HMC by a phagocyte-directed action. Adhesion was markedly inhibited by MAb against CD18 and CD11b, with lesser or no inhibition being afforded by MAb against CD11a, CD11c, or ICAM-1. In contrast, prolonged exposure of HMC to TNF or IL-1 (1-18 h) increased HMC adhesiveness for phagocytes. These actions were blocked by actinomycin D or cycloheximide and by MAb against HMC ICAM-1 or phagocyte CD18, CD11a, or CD11b, suggesting that cytokines provoked adhesion by inducing HMC ICAM-1 synthesis. In keeping with this interpretation, TNF treatment of HMC was associated with increased ICAM-1 surface expression, as determined by indirect immunofluorescence, and increased ICAM-1 mRNA levels, as determined by Northern blot analysis. The actions of TNF on phagocytes and HMC were additive. HMC injury, as determined by 51Cr release, was only observed when both phagocytes and HMC were activated by TNF. HMC injury was attenuated by anti-CD18 MAb and superoxide dismutase, suggesting that the injury process was, in part, adhesion dependent and mediated by reactive oxygen species.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytokine-induced phagocyte adhesion to human mesangial cells: role of CD11/CD18 integrins and ICAM-1. 172 95

The administration of a high-dose of a serine protease inhibitor is recommended in patients complicated by multiple organ failure (MOF), including adult respiratory distress syndrome (ARDS), induced by acute pancreatitis. The accumulation of polymorphonuclear leukocytes (PMN) in affected organs is considered to be one of the causative factors of MOF. Adhesion to endothelial cells (EC), via adhesion molecules, and the transendothelial migration of PMN is closely associated with the accumulation of PMN. We examined the effects of two serine protease inhibitors, ulinastatin (UT) and gabexate mesilate (GM), on EC-PMN adhesion and transendothelial migration in human umbilical vein EC and 51Cr-labeled PMN in vitro. EC-PMN adhesion, and the expression of intercellular adhesion molecule-1 (ICAM-1) and endothelial cell adhesion molecule-1 (ELAM-1) on EC induced by IL-1 beta and TNF alpha, were reduced by the pretreatment of EC with these inhibitors. The transendothelial migration of PMN stimulated by IL-8 was also inhibited by pretreating PMN with UT or GM. We also examined whether these inhibitors reduced PMN accumulation in the lung in rats with acute pancreatitis induced by a closed duodenal loop. The myeloperoxidase activity in and histological findings of the lung suggested that UT and GM reduced PMN accumulation. In conclusion, serine protease inhibitors may inhibit PMN accumulation in ARDS due to acute pancreatitis.
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PMID:Effects of serine protease inhibitors on accumulation of polymorphonuclear leukocytes in the lung induced by acute pancreatitis in rats. 764 5

Self-renewal and differentiation of B-cell precursors is dependent on interactions with bone marrow (BM) stromal cells and associated extracellular matrix. We have recently developed an interleukin (IL)-7-dependent, BM-derived stromal cell culture that supports the growth of normal human B-cell precursors. In the current study, we have characterized the constitutive expression, cytokine-regulated expression, and function of adhesion molecules on BM stromal cells that are critical for adhesion of B-cell precursors. Flow cytometric analysis showed that cultured adult BM stromal cells expressed higher constitutive levels of vascular cell adhesion molecule (VCAM)-1 than intercellular adhesion molecule (ICAM)-1 (CD54). IL-1 beta upregulated VCAM-1 and CD54 in a dose-dependent manner, whereas IL-4 upregulated VCAM-1, but had no effect on CD54. In contrast, transforming growth factor (TGF)-beta decreased the level of BM stromal cell VCAM-1. Using an assay to measure the adhesion of 51Cr-labeled B-cell precursors to BM stromal cells, we observed a direct correlation between cytokine-regulated levels of VCAM-1 and the capacity of stromal cells to support the adhesion of B-cell precursors. Blocking studies using a panel of monoclonal antibodies (MoAb) showed that adhesion of B-cell precursors to untreated and cytokine-treated (IL-1 beta, IL-4) BM stromal cells was mediated by very late antigen (VLA)-4 (CD49d/CD29) and VCAM-1. Adhesion of B-cell precursors could also be enhanced by direct stimulation with MoAb to the CD29 subunit. Our collective results indicate that B-cell precursor/BM stromal cell adhesion is mediated by a VLA-4-VCAM-1 interaction, which in turn can be regulated at the level of the BM stromal cell by cytokines that specifically increase or decrease cell surface VCAM-1.
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PMID:Regulation of human B-cell precursor adhesion to bone marrow stromal cells by cytokines that exert opposing effects on the expression of vascular cell adhesion molecule-1 (VCAM-1). 768 14

Adhesion molecules involved in attachment between human pancreatic carcinoma and activated endothelial cells in vitro were investigated. Basal adhesion occurred between 6 pancreatic carcinoma cell lines and unstimulated human umbilical vein endothelial cells (HUVEC), and augmented basal adhesion to activated HUVEC was only seen when pancreatic cancer cells expressed sialyl Lewisa (SLea) and sialyl Lewisx (SLex). Activation of HUVEC with interleukin 1-beta (IL-1 beta) or tumor necrosis factor-alpha (TNF-alpha), but not with interferon-gamma (IFN-gamma), generated the augmentative basal adhesion. Dose dependence and additive effect were observed in augmentation of the basal adhesion induced by IL-1 beta and/or TNF-alpha. Increase in adhesion correlated with up-regulation of the surface E-selectin (or ELAM-1) on HUVEC, and was evident at both 25 degrees C and 4 degrees C. Anti-E-selectin and anti-SLea blocked the augmented attachment, whereas anti-SLex, an antibody against another known ligand for E-selectin, did not. The collective evidence indicates that attachment between pancreas carcinoma cells and activated endothelial cells is regulated by cytokines such as IL-1 beta and TNF-alpha, and is mediated by SLea on pancreas carcinoma and E-selectin on endothelial cells. These molecules may be of significant importance in blood-borne metastasis of pancreatic carcinoma cells to inflamed sites.
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PMID:Importance of E-selectin (ELAM-1) and sialyl Lewis(a) in the adhesion of pancreatic carcinoma cells to activated endothelium. 768 90

We have previously shown that lymphocytic cells bind to cultured syncytiotrophoblast and that this may be important in the lymphocyte-mediated infection of trophoblast with the human immunodeficiency virus (HIV). Leukocyte-trophoblast adhesion may also have implications for normal trophoblast function. The following experiments were designed to characterize the adhesion systems that mediate the attachment of lymphocytic cells to trophoblast. Adhesion was assayed by labelling lymphocytic MOLT-4, clone 8 cells with the fluorescent marker, calcein-AM, and then incubating them with primary cultures of human syncytiotrophoblast. Adhesion was stimulated by pretreatment of the trophoblast cultures with several cytokines either alone or together. These included tumor necrosis factor-alpha (TNF-alpha), granulocyte/macrophage-colony stimulating factor (GM-CSF), interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN-gamma). Stimulation was time- and dose-dependent. In contrast, preincubation of trophoblast cultures with anti-TNF-alpha antibodies for 2 days reduced MOLT adhesion by almost 50%. Preincubation with other anti-cytokine antibodies had no significant effect on adhesion. In other experiments, adhesion was measured in the presence of antibodies to known adhesion molecules. Adhesion was reduced by 50% in the presence of antibodies to alpha 4 integrin or beta 1 integrin. When present together, these antibodies reduced adhesion by almost 85%. Incubation in the presence of antibodies to the very late activation antigen-4 (VLA-4; alpha 4 beta 1 integrin) counter-receptors, VCAM-1 and CS-1, was without effect. Adhesion was also unaffected by antibodies to LFA-1, ICAM-1, ICAM-2, LFA-2, or LFA-3. These results suggest that adhesion is mediated by an adhesion system consisting of lymphocyte VLA-4 (alpha 4 beta 1) and an as yet unidentified counter receptor on trophoblast.
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PMID:Effect of cytokines and anti-adhesion molecule antibodies on the adhesion of lymphocytic cells to human syncytiotrophoblast. 780 71

Adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and its counter-receptor, lymphocyte function associated antigen-1 (LFA-1), play very important roles in immune responses. In this study, the effects of cytokines on cultured human melanoma cells (MMG2) were examined, especially focussing on the expression of ICAM-1 on MMG2 and lymphocyte adhesion to MMG2. Both the expression of ICAM-1 and HLA-DR on MMG2 increased after treatment with IFN-gamma. ICAM-1 expression began to increase earlier than HLA-DR expression. TNF-alpha and IL-1 beta also increased the expression of ICAM-1 on MMG2. However, these cytokines did not increase the expression of HLA-DR. IFN-gamma had a dose dependent effect on lymphocyte adhesion to MMG2. Pretreatment of IFN-gamma treated MMG2 with 84H10 (anti-ICAM-1 antibody) or pretreatment of lymphocytes with either SPV-L7 (anti-LFA-1 alpha antibody) or IOT10 (anti-LFA-1 beta antibody) inhibited the lymphocyte adhesion to MMG2. These results suggest that ICAM-1 molecules induced on melanoma cells by IFN-gamma can interact with LFA-1 molecules on lymphocytes.
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PMID:Intercellular adhesion molecule-1 on cultured human melanoma cells: influence of cytokines. 809 20

We determined the ability of proinflammatory cytokines to enhance ICAM-1 (CD54) expression on, and PBMC adhesion to, human synoviocytes. Surface molecules were characterized by cell ELISA and by flow cytometry. Adhesion of PBMC to synoviocyte monolayers was measured by direct counting or by colorimetric staining. Most cytokines upregulated ICAM-1 expression (IL-1 beta > TNF alpha > IFN-gamma >> PDGF-bb, IL-6), but not GM-CSF or TGF beta. A similar concentration-dependent increase was observed for synoviocytes derived from patients with rheumatoid or osteoarthritis. Kinetic studies of ICAM-1 expression differed among several cytokines: an early rise with IL-1 beta or TNF alpha stimulation, a gradual increase with IFN-gamma, a transient increase with PDGF-bb, and a plateau with IL-6. Adhesion of PBMC to synoviocytes was increased by IL-1 beta or TNF alpha and reduced by MAb to CD54 or CD18. Increased synoviocyte adhesiveness may promote interactions with infiltrating inflammatory cells.
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PMID:Proinflammatory cytokines enhance human synoviocyte expression of functional intercellular adhesion molecule-1 (ICAM-1). 810 22

Basic fibroblast growth factor (bFGF) may act to modulate hematopoiesis in addition to its effects on mesenchymal cells. We studied the effects of bFGF on human and murine primary marrow megakaryocytes. bFGF modestly enhanced the size of the human megakaryocyte colony-forming unit (CFU-MK) and cell numbers per colony, in combination with interleukin-3 (IL-3) or granulocyte-macrophage colony stimulating factor (GM-CSF). Adhesion of human megakaryocytes to bone marrow (BM) stromal fibroblasts was enhanced when either stromal fibroblasts or megakaryocytes were treated with bFGF. This resulted in significantly increased proliferation of megakaryocytes. In addition, bFGF augmented secretion of the cytokines tumor necrosis factor alpha and IL-6 by human primary BM megakaryocytes. Immature murine megakaryocytes showed a significant growth response to bFGF as measured by the single cell growth assay. This effect was abrogated by specific antibodies for bFGF and combination of anti-IL-6 and anti-IL-1 beta antibodies. bFGF has no effect on murine CFU-MK formation, but significantly potentiated CFU-MK formation in the presence of IL-3 or GM-CSF. These results indicate that the effect of bFGF on various megakaryocyte populations is different and that bFGF may affect megakaryocytopoiesis via modulation of megakaryocyte-stromal interactions and via augmentation of cytokine secretion from megakaryocytes.
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PMID:Modulation of megakaryocytopoiesis by human basic fibroblast growth factor. 816 81

Cell-cell adhesion is essential for many immunological functions and is believed to be important in the regulation of hematopoiesis. Adhesive interactions between human endothelial cells and megakaryocytes were characterized in vitro using the CMK megakaryocytic cell line as well as marrow megakaryocytes. Although there was no adhesion between unactivated human umbilical vein endothelial cells (HUVEC) and megakaryocytes, treatment of HUVEC with inflammatory cytokines such as IL-1 beta, tumor necrosis factor alpha, INF-gamma, or the phorbol ester phorbol myristate acetate (PMA) resulted in a time- and dose-dependent increase in adhesion. Stimulation of marrow megakaryocytes or CMK cells with the cytokines IL-1 beta, GM-CSF, IL-6, IL-3, or PMA augmented their adhesion to endothelium. Monoclonal antibodies against the LFA-1 subunit of the leukocyte adherence complex CD18 inhibited the binding of marrow megakaryocytes or CMK cells to HUVEC. Adhesion blocking experiments also demonstrated that the VLA-4/VCAM-1 pathway was important for megakaryocyte attachment to HUVEC. Adhesion promoted maturation of megakaryocytic cells as measured by increased expression of glycoproteins GpIb and GpIIb/IIIa and by increased DNA content. These observations suggest that alterations in megakaryocyte adhesion may occur during inflammatory conditions, mediated by certain cytokines, resulting in augmented megakaryocyte maturation.
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PMID:Characterization of adhesive interactions between human endothelial cells and megakaryocytes. 851 51


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