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)

The beta 1 integrin family, major adhesive receptors for the extracellular matrix (ECM), have been reported to be present in normal and diseased kidneys. Attachment of glomerular cells to ECM is mediated by beta 1 integrins. Several members of the beta 1 integrins are referred to as VLA (very late activation) antigens. Peripheral mononuclear cells also express VLA antigens in both resting and activated states. We examined the expression and function of VLA antigens on peripheral lymphocytes and monocytes in patients with IgA nephropathy using monoclonal antibodies (mAbs) specific for VLA alpha-chains. Peripheral lymphocytes from patients with IgA nephropathy expressed VLA-4 alpha and 5 alpha, but not VLA-1 alpha, 2 alpha or 3 alpha. Peripheral monocytes from patients with IgA nephropathy expressed VLA-2 alpha, 4 alpha and 5 alpha, but not VLA-1 alpha or 3 alpha. The expression of VLA adhesive receptors was observed in healthy individuals. Adhesion assay to fibronectin revealed augmented adhesion of mononuclear cells in IgA nephropathy (P < 0.05), and this increased adhesion was inhibited by mAbs to VLA-4 alpha and 5 alpha. The expression of beta 1 integrins in IgA nephropathy was similar to that of healthy individuals, but the function of these molecules in terms of adhesion to fibronectin though VLA-4 and VLA-5 is increased in these patients. These findings suggest that the activation of fibronectin receptors on peripheral mononuclear cells plays an important role in the pathogenic process of IgA nephropathy.
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PMID:Expression and function of fibronectin receptors on peripheral mononuclear cells in IgA nephropathy. 853 24

Adhesion molecules are involved in cell-cell interactions and therefore probably play a role in the differentiation and egress of cells from the bone marrow, which might be potentially important in the biology of acute promyelocytic leukemia (APL). All-trans retinoic acid (ATRA) is known to induce in vitro and in vivo differentiation of APL cells and to favor their release from the bone marrow into the blood at initiation of therapy. In order to determine whether these effects might be mediated in part by modifications of beta1-integrin and pseudoimmunoglobulin expression on APL cells, the expression of these adhesion molecules on bone marrow (BM) blast cells from 24 APL patients was assayed at diagnosis by an indirect immunofluorescence method. CD49b, CD49d, CD49e, CD49f, CD54, CD58, and CD56 were expressed respectively on 18%+/-20% (0-66%), 40%+/-31% (0-96%), 48%+/-32% (0-97%), 29%+29% (1-94%), 51%+/-30% (5-98%), 37%+/-24% (1-85%) and 32%+/-31% (0-97%) of APL cells, with respectively 39%, 71%, 79%, 50%, 70%, 70%, and 53% positive cases (> or = 20% positive cells). Despite a wide variability between individual samples, the expression of beta1-integrins and that of pseudo-immunoglobulins tended to be higher in APL in comparison with that of a cohort of 63 patients with other AML subtypes with significant differences for CD54 expression (51%+/-30% vs 28%+/-27%, P=0.006) and CD56 expression (37%+/-24% vs 17%+/-19%, P=0.0003). An in vitro differentiation assay was performed in nine cases. Cells were harvested after 4-7 days of culture and studied for the expression of adhesion molecules. Granulocytic differentiation was marked by persistence of CD15 expression. Antigen expression was decreased after culture with ATRA for all beta1-integrins (except CD49b and CD49f) and pseudoimmunoglobulins (except CD54) tested. However, changes were statistically significant only for CD56 (P=0.04), CD49d (P=0.02) and CD49e (P=0.01). The modifications in the expression of the beta1-integrins and pseudo immunoglobulins were not specific to ATRA-induced differentiation, but commonly observed with differentiation. Furthermore, the modifications in the adhesive properties of APL cells to extracellular matrix proteins, observed on adhesion assays, were not statistically significant after ATRA-induced differentiation. Overall, the level of expression of beta1-integrins and pseudo-immunoglobulins was higher in APL than in other AML subtypes, and appeared modified with induced differentiation. This was not specific of ATRA, but might be involved in the general differentiation phenomenon. The modulation of adhesion molecules does not seem a sufficient requisite for the development of the retinoic acid syndrome, but could nevertheless be part of the increase in leukocyte counts observed during the first days of ATRA therapy.
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PMID:Expression of beta1-integrins and pseudo-immunoglobulins on acute promyelocytic leukemia cells and its modifications during in vitro differentiation. 958 81

Both macrophages (MAC) and dendritic cells (DC) are members of the mononuclear phagocyte system (MPS) with monocytes (MO) as common precursor cells. Cells of the MPS are able to take up, process and present antigens to T lymphocytes, thereby inducing a primary or secondary immune response. Adhesion molecules are of crucial importance for the interaction of antigen-presenting cells with immune cells, especially T lymphocytes. By representational difference analysis, we identified CD49c (VLA-3), a member of the beta1-integrin family of adhesion receptors, as differentiation-associated antigen in MO-derived MAC. In contrast, MO-derived DC did not express CD49c mRNA. These data prompted us to compare the integrin expression pattern of MAC and DC. Both cell types showed a low expression of the alpha-chains of the beta1-integrins CD49a, CD49b, CD49d and CD49e, whereas a marked difference was observed for CD49c and CD49f. Expression of both integrins increased during MO to MAC differentiation, but was not detectable on DC. In parallel the beta1-chain (CD29) was clearly up-regulated during MO to MAC differentiation but was only weakly expressed on DC. On the other hand, the beta2-integrins CD11a, CD11b, CD11c and CD18 were all expressed on MAC and DC. Beside their role in cell-cell interaction and adhesion, beta2-integrins are also known as possible binding molecules for bacteria and lipopolysaccharide (LPS), especially for high LPS concentrations. Therefore we investigated the LPS response of MAC versus DC in terms of tumour necrosis factor-alpha (TNF-alpha) release. DC were less responsive to low doses of LPS, which can easily be explained by the very low CD14 expression on DC compared for MAC. In contrast, the TNF-alpha response was comparable to MAC when DC were stimulated with high LPS concentrations. Our results show a specific, differentiation-dependent pattern of beta1- and beta2-integrin expression on in vitro-generated MAC and DC. We suggest that the high expression of CD11/CD18 on DC could be involved in the LPS binding of DC. As LPS is not only an activation but also a differentiation stimulus for DC, the expression of CD11/CD18 on DC may be important for the successful maturation of DC and thereby the initiation of a primary immune response.
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PMID:Comparative analysis of integrin expression on monocyte-derived macrophages and monocyte-derived dendritic cells. 1092 59

The study was designed to investigate the changes, both numerically and functionally, of the molecules critical to wound healing in spinal cord injury (SCI) patients. Spinal cord injury patients who demonstrated delayed healing of their pressure ulcers were used as study subjects. Age-matched healthy individuals served as controls. Adhesion molecule expression of the peripheral blood leukocytes, including lymphocytes and granulocytes, was measured by flow cytometric analysis. Binding capacity of the lymphocytes was evaluated using human umbilical cord vein endothelial cells (HUVECs) as the binding matrix. Samples from pressure ulcers of the patients were immunostained to define fibronectin, kalinin, beta4 integrin, alpha2beta1, alpha3beta1, alpha5beta1, and CD138 expression. Compared to healthy controls, there was decreased expression of CD11a, CD11b, CD18, CD49b, CD49c, CD49d, CD54, and CD8 in patients' lymphocyte populations and CD11a, CD18, CD49c, CD49d, and CD8 in patients' granulocyte populations. The binding capacity, expressed as percentage binding of the lymphocytes to the HUVEC matrix, was greatly diminished in the patients. There was markedly diminished immunohistochemical staining of fibronectin in pressure ulcers. These findings showed that delayed healing of pressure ulcers in SCI patients can be attributed to reduced adhesion molecule expression, impaired cell-cell interaction, and lack of extracellular matrix structural and functional protein.
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PMID:Cellular and molecular alterations in spinal cord injury patients with pressure ulcers: a preliminary report. 1189 Jul 21

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Adhesion molecules play important roles in cell-cell and cell-extracellular matrix (ECM) interactions in inflammation. Blocking the interaction between inflammatory cells and vascular endothelia can prevent cell entry into tissues and harmful inflammatory responses, that is, autoimmunity, but could also limit immunosurveillance by anti-viral T cells in sites of infection or latency. Development of progressive multifocal leukoencephalopathy in patients treated with antibody against very late antigen (VLA)-4 prompted us to explore an alternative therapeutic approach. We used an antibody against the integrin alpha2, VLA-2, that interacts with ECM, not vascular endothelium. SJL/J mice were sensitized with myelin proteolipid protein (PLP)(139-151) peptide to induce experimental autoimmune encephalomyelitis (EAE), an animal model for MS. Treatment of mice with VLA-2 antibody suppressed clinical signs and CNS inflammation of EAE, when antibody was given immediately after disease onset. In contrast, VLA-4 or VLA-2 antibody treatment of mice during the priming or remission phase of EAE had minor effects on the disease's clinical course. No differences were found in lymphoproliferative responses to PLP(139-151) among treatment groups. Data suggest that blocking cell-ECM interactions can be an alternative therapy for MS.
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PMID:Modulation of experimental autoimmune encephalomyelitis by VLA-2 blockade. 1749 37

Culture-expanded human mesenchymal stem cells (hMSCs) are increasingly used in a variety of preclinical and clinical studies. However, these cells have a low rate of engraftment to bone marrow or damaged tissues. Several laboratories have shown that during isolation and subculturing mesenchymal stem cells quickly lose the expression of CXCR4, the key receptor responsible for lymphocytes and hematopoietic stem cell homing. Here we show that culturing of hMSCs as three-dimensional aggregates (hMSC spheroids) restores CXCR4 functional expression. Expression of CXCR4 inversely correlates with the secretion of SDF-1 by hMSCs. Cells from hMSC spheroids up-regulate expression of CD49b, the alpha2 integrin subunit, and suppress the expression of CD49d, the alpha4 integrin subunit. Transfer of cells from the spheroids back to a monolayer suppresses the expression of CXCR4 and CD49b and restores the expression of CD49d. Treatment of cells from the spheroids with SDF-1 leads to CXCR4 internalization and activation of ERK-1,2. Adhesion of hMSCs to human umbilical vein endothelial cells (HUVECs) was investigated. SDF-1, AMD-3100, or exposure of HUVECs to hypoxia did not affect adhesion of hMSCs from a monolayer to HUVECs. Adhesion of cells from hMSC spheroids to HUVECs was stimulated by SDF-1, AMD-3100, or by exposure of HUVECs to hypoxia. Stimulatory effects of hypoxia and addition of SDF-1 or AMD-3100 were not additive. Overall, our data indicate that the expression of CXCR4 by hMSCs regulates hMSC adhesion to endothelial cells.
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PMID:Culturing of human mesenchymal stem cells as three-dimensional aggregates induces functional expression of CXCR4 that regulates adhesion to endothelial cells. 1833 85

Adhesion molecules are receptors found on the surface of leukocytes and endothelial cells, which bind to their ligands, either on other cells or on the extracellular matrix. The function of adhesion molecules is to allow leukocytes to interact with other hemopoetic cells or with foreign antigens (Ags) in the blood, to transiently adhere to the vascular endothelium, to migrate between endothelial cells and through the basement membrane into the surrounding tissue, and to adhere to the epithelium. There are three main groups of adhesion molecules: the integrins, immunoglobulin (Ig) supergene family, and the selectins: These are summarized in Table 1 (1-7). Table 1 Summary of Adhesion Molecules Group CD number Name Expressed on Ligand Integrins CD 49a VLA-1 T lymphocytes, fibroblasts, basement membrane Laminin, collagen B1 very late antigens CD 49b VLA-2 Activated T lymphocytes, platelets, fibroblasts, endothelium, epithelium Collagen, laminin CD 49c VLA-3 Epithelium, fibroblasts Laminin, collagen, fibronectin CD 49d VLA-4 Leukocytes, fibroblasts VCAM-1, fibronectin CD 49e VLA-5 Leukocytes, platelets, epithelium Fibronectin CD 49f VLA-6 T lymphocytes, platelets Laminin B2 leukocyte integrins CD 11a LFA-1 Leukocytes ICAM-1, ICAM-2, ICAM-3 CD 11b Mac-1 Macrophages, monocytes, granulocytes ICAM-1, fibrinogen, C3bi CD 11c p150.95 Macrophages, monocytes, granulocytes Fibrinogen, C3bi IG Supergene family CD 54 ICAM-1 Endothelium, leukocytes, epithelium LFA-1 Mac-1 CD 102 ICAM-2 Endothelium, leukocytes LFA-1 CD 106 VCAM-1 Endothelium, dendritic cells, tissue macrophages VLA-4 Selectins CD 62E E selectin Endothelium Sialyl Lewis x CD 62P P selectin Platelets, endothelium Sialyl Lewis x CD 62L L selectin Leukocytes Mannose-6-P, fructose-6-P.
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PMID:Immunohistochemical analysis of adhesion molecules in airway biopsies. 2131 33


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