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 and cytokines are involved in regulation of cellular host responses in infection processes. In this study the roles of the integrins Mac-1 and VLA-4, as well as those of the cytokines tumor necrosis factor alpha (TNF-alpha) and gamma interferon (IFN-gamma), in defense mechanisms against Yersinia enterocolitica in Peyer's patches (PP) and mesenteric lymph nodes (MLN) were investigated by blocking these molecules with antibodies in vivo prior to orogastric Yersinia infection. Intestinal Yersinia infection caused abscesses composed of polymorphonuclear (Mac-1+ VLA-4+ Pgp-1+ ICAM-1-) and mononuclear (Mac-1+ VLA-4+ Pgp-1+ ICAM-inhibited phagocytosis of yersiniae by macrophages, (ii) reduced Yersinia-specific proliferation and IFN-gamma production of T cells from PP and MLN, and (iii) caused increased bacterial growth in PP and MLN followed by profound tissue destruction. Neutralization of TNF-alpha or IFN-gamma had comparable effects, suggesting that cell-mediated host responses including activated macrophages are required for control of yersiniae in intestinal tissues. The number of Mac-1+ cells in PP and MLN increased after yersinia infection, and recruitment of these cells was not blocked by administration of anticytokine or anti-integrin antibodies. While anti-VLA-4, -TNF-alpha, or -IFN-gamma antibody treatment caused an increased dissemination of yersiniae from PP to the spleen systemic dissemination was reduced by anti-Mac-1 antibodies. The results of this study suggest that the cytokines IFN-gamma and TNF-alpha as well as the integrins Mac-1 and VLA-4 are involved in protective cellular host defense mechanisms in PP and MLN against Y. enterocolitica, the latter probably being involved in both cell-cell and cell-pathogen interactions.
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PMID:Defense mechanisms in Peyer's patches and mesenteric lymph nodes against Yersinia enterocolitica involve integrins and cytokines. 860 1

Semliki Forest virus A7 (SFV-A7) is a neurotropic alphavirus that leads to an asymptomatic encephalitis in adult immunocompetent mice. We studied the expression of leukocyte and endothelial cell adhesion molecules in the spleen and in the central nervous system (CNS) during SFV-A7 infection. Kinetics of the expression of LFA-1 alpha/CD11a, LFA-1 beta/CD18, Mac-1/CD11b, VLA-4/CD49d, ICAM-1/CD54 and L-selectin/CD62L was determined on splenic CD4+ and CD8+ T-cells and macrophages by flow cytometry. Time course of the expression of these antigens and VCAM-1/CD106 as well as viral antigens in the CNS was studied by immunoperoxidase staining. In the spleen, a sustained increase in LFA-1-expression and a temporary increase at day 7 in the expression of VLA-4, Mac-1 and ICAM-1 were detected on CD8+ T-cells. L-selection was down-regulated on CD4+ cells. Adhesion molecules on macrophages remained unchanged. In the CNS, expression of Mac-1+, VLA-4+ and LFA-1+ cells increased in parallel with the kinetics of the expression of their ligands ICAM-1 and VCAM-1 on brain vessels. Upregulation of adhesion of molecules peaked between days 5-8 and was most prominent in the cerebellar and brain stem white matter where viral antigens were most abundant. We conclude that the adhesion molecules profile of splenic T cells is altered during SFV-A7 infection which may influence their homing into the CNS. Macrophages are probably recruited non-specifically as a consequence of activation of the brain vascular endothelium in the inflamed areas of the brain.
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PMID:Semliki Forest virus infection leads to increased expression of adhesion molecules on splenic T-cells and on brain vascular endothelium. 937 56

The article provides a review of the role of granulocyte colony-stimulating factor (G-CSF) for mobilization and transplantation of peripheral blood progenitor and stem cells. Recombinant gene technology has permitted the production of highly purified material for therapeutic use in humans. Progenitor cells can be assessed using semisolid and liquid culture assays or direct immunofluorescence analysis of cells expressing CD34. This antigen is found on lineage-determined hematopoietic progenitor cells as well as on more primitive stem cells with extensive self-renewal capacity. Administration of G-CSF during steady-state hematopoiesis or following cytotoxic chemotherapy leads to an increase of hematopoietic progenitor cells in the peripheral blood. The level of circulating CD34+ cells post-chemotherapy is greater compared with G-CSF administration during steady state. On the other hand, CD34+ cells harvested post-chemotherapy contain a smaller proportion of more primitive progenitor cells (CD34+/HLA-DR- or CD34+/CD38-) compared with G-CSF treatment alone. Independent of the mobilization modality, the amount of previous cytotoxic chemo- and radiotherapy adversely affects the yield of hematopoietic progenitor cells. While continuous subcutaneous administration of G-CSF between 5 and 16 micrograms/kg bodyweight is preferred, additional dose-finding studies may be helpful to optimize current dose schedules. Adhesion molecules like L-selectin, VLA (very late antigen)-4 and LFA (leukocyte function antigen)-1 are likely to play a role in mobilization, since these antigens are expressed on CD34+ cells from bone marrow in different densities compared with blood-derived CD34+ cells collected following G-CSF-supported cytotoxic chemotherapy. It is also relevant for transplantation that during G-CSF-enhanced recovery post-chemotherapy, peripheral blood is enriched with a greater proportion of CD34+ cells expressing Thy-1 in comparison with CD34+ cells from bone marrow samples obtained on the same day or before the mobilization therapy was started. The early nature of the CD34+/Thy-1+ cells is very likely since this phenotype has been found on stem cells from human fetal liver and bone marrow and on cord blood cells. As a result, G-CSF-mobilized blood stem cells provide rapid and sustained engraftment following high-dose therapy, including myeloablative regimens. Positive selection of CD34+ cells as well as ex vivo expansion using different cytokines are currently being investigated for purging and improvement of short-term recovery post-transplantation. Future developments include the use of blood-derived hematopoietic stem cells for somatic gene therapy. The availability of growth factors has been an important prerequisite for the development of these new avenues for cell therapy.
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PMID:The role of granulocyte colony-stimulating factor in mobilization and transplantation of peripheral blood progenitor and stem cells . 938 79

The integrin VLA-4 (alpha4 beta1) is a receptor for fibronectin and vascular cell-adhesion molecule 1 (VCAM-1). Four functionally different epitopes, designated A, B1, B2 and C, have previously been defined on the alpha4 subunit. Using K562 alpha4 mutant transfectants we found that alpha4 amino acids Tyr151, Gln152, Asp153, Tyr154 and Val155 are important for the structure of the epitope B2. Mutations at alpha4 Gln152 substantially impaired the transfectant adhesion to a CS-1-containing fragment of fibronectin (FN-H89), whereas this adhesion was not affected on the other alpha4 mutant transfectants. None of the alpha4 mutations significantly altered the adhesion of the different alpha4 transfectants to VCAM-1. In addition, we have identified residues Gln152, Asp153 and Tyr154 as part of the alpha4 epitope B2 involved in homotypic cell aggregation. The decrease in adhesion to FN-H89 shown by Gln152 alpha4 mutant transfectants was the result of an inefficient binding of FN-H89 by VLA-4 mutated at this residue. Also, mutant VLA-4 displayed an altered reactivity with HUTS-21, an anti-beta1 monoclonal antibody that reacts with functionally active VLA integrins. Adhesion to FN-H89 was not restored unless stimuli that increase the ligand-binding affinity of VLA heterodimers were added, suggesting that cell adhesion was affected in the initial phases. These results indicate that alpha4 Gln152 modulates cell adhesion to FN-H89 by playing important roles in the maintenance and/or the acquisition of an active state of VLA-4, an integrin that is normally expressed on the cell surface in a range of multiple activation states. The location of the alpha4 Gln152 residue on a loop of the upper surface of the proposed beta-propeller structure suggests a close association with potential ligand-binding sites.
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PMID:A novel region of the alpha4 integrin subunit with a modulatory role in VLA-4-mediated cell adhesion to fibronectin. 958 49

Cultures of endothelial (En) cells derived from human brain microvessels were established in order to characterize adhesion molecule expression and to assay the adhesion properties of neoplastic cell lines to monolayers of En cells. Low constitutive expression of beta1 integrin (CD29), and ICAM-2 (CD102) was detected on human brain microvessel En cells. The beta1 chain of the VLA integrin family, ICAM-1, E-selectin (CD62E) and VCAM-1 (CD106) but not ICAM-2 and PECAM-1 (CD31) expression was upregulated by IL1-alpha, and TNF-alpha proinflammatory cytokines. High expression of PECAM-1 was found on non-activated human brain EN cells. In order to study the potential role of adhesion molecules in neoplastic cell adhesion two tumor cell lines were chosen. Adhesion of a cell line (DU145) derived from a cerebral metastasis of prostate carcinoma to human brain microvessel En cell monolayers was less pronounced compared to adhesion of a primary prostate carcinoma cell line (ND1). Adhesion of cerebral metastatic neoplastic cell line (DU145) was not significantly influenced by incubation of endothelial cells with different proinflammatory cytokines. The adhesion capability of primary prostate carcinoma line (NDI) was significantly upregulated by TNF-alpha proinflammatory cytokine. Furthermore, the adhesion of ND1 was partly inhibited using anti-E-selectin and VCAM-1 monoclonal antibodies. There was no significant effect of anti-adhesion antibodies on the adhesion characteristics of the cerebral metastatic (DU145) cell line. Our data demonstrate that different mechanisms are involved in the adhesion of neoplastic cells to cerebral En cells and turn our attention to the importance of adhesion molecule expression in the formation of metastases.
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PMID:Influence of adhesion molecule expression by human brain microvessel endothelium on cancer cell adhesion. 972 32

To analyze adhesion molecule expression on peripheral blood mononuclear cells (PBMCs) and on different lymphocyte subpopulations (CD2+, CD8+, CD19+, and CD56+ subsets) in chronic alcoholism, 30 well-nourished chronic alcoholics without ethanol-related diseases and 30 matched controls were included in the study. Adhesion molecules that mediate adhesion to other cells and to extracellular matrix proteins, and whose cellular expression is modified during lymphocyte activation, were selected for study. A detailed clinical evaluation, laboratory analysis, nutritional assessment, and study of adhesion molecule expression was performed. A significant higher expression of CD29 (beta1-integrin) (p = 0.001), VLA-3 (p = 0.002), VLA-4 (p = 0.03), and VLA-5 (p = 0.001) were observed on PBMCs of chronic alcoholics, compared with control subjects, whereas no changes were observed in CD18 (beta2-integrin) and CD50 (ICAM-3) expression. The upregulation of CD29 and VLA proteins only affected T lymphocytes (CD2+/CD8+/CD4+ cells). These data confirm that T cells of chronic alcoholics are basally activated and that changes in adhesion molecule expression on PBMCs may be responsible of disturbances of adhesion processes in chronic alcoholics without ethanol-related diseases.
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PMID:Upregulated expression of VLA proteins and CD29 in peripheral blood lymphocytes of chronic alcoholics without ethanol-related diseases. 1006 70

Adhesion molecules are critical in the cellular interactions involved in specific immune responses. They are used for homing, cell migration, cell-cell contact and, in some cases, for the delivery of costimulatory signals. Since the host-versus-graft (HVG) reaction represents a particular form of T-B-cell interaction, we have explored whether the inhibition of lymphocyte function-associated antigen-1/intracellular adhesion molecule-1 (LFA-1/ICAM-1) interactions and the signalling through very late activation antigen-4 (VLA-4) have any effect on the development of a lupus-like disease in BALB/c mice injected at birth with (BALB/cxC57BL/6)F1 spleen cells. In close association with the development of tolerance to donor allografts, these mice show a polyclonal activation of F1 donor B cells by alloreactive host CD4+ T cells, manifested by the production of autoantibodies (autoAbs) and the development of a mild glomerulonephritis. The dose of the monoclonal antibody (mAb) employed has been adjusted to block completely the molecule on the surface of peripheral lymphocytes without interfering with the induction of neonatal tolerance. Injection of saturating doses (100 microg/2 days) of either anti-LFA-1alpha or anti-ICAM-1 mAbs, but not anti-VLA-4alpha or anti-LFA-1beta mAbs, blocks the production of anti-ssDNA autoAbs and the thrombocytopenia characteristic of this HVG disease (HVGD). However, anti-VLA-4alpha treatment is only able to delay the production of autoAbs and the anti-LFA-1beta treatment, not to modify the evolution of the HVGD. These results point to the relevance of LFA-1/ICAM-1 interactions, but not of the VLA-4-mediated signal, in the polyclonal B-cell activation occurring during the allogeneic interactions between host T helper type 2 cells and donor B cells in HVGD.
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PMID:Different roles for LFA-1 and VLA-4 integrins in T-B-cell interactions in vivo. 1044 65

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

CD1a(pos) dendritic cells (DCs) and Langerhans cells (LCs) are highly specialized antigen-presenting cells mainly localized in the skin. Various cells have been identified as precursors of cutaneous DCs, but the definitive precursor subpopulations remain to be defined and characterized in detail. In this study, DCs were generated in vitro from monocytes (monocyte-derived DCs, MoDCs) and from CD34(pos) stem cells (CD34(pos) cell-derived DCs, CD34DCs). By virtue of their CD14 and CD1a expression, four CD34DC subpopulations were characterized while MoDCs contain three different subpopulations. Of these, CD14-expressing cells are considered to be precursors of fully differentiated DCs, which themselves are CD14(neg)CD1a(pos). Both, MoDCs and CD34DCs expressed the alpha integrins LFA-1, Mac-1, CR4, VLA-4, VLA-5 and the beta2 integrin CD18. CD34DCs and MoDCs were negative for VLA-3, whereas MoDCs, but not CD34DCs expressed VLA-6. Phenotypic and functional characterization of the cells generated herein at earlier time points revealed that DCs at day 3 of culture may reflect the in vivo situation more closely than at day 7. Adhesion of DC precursors to endothelial cells and to components of the extracellular matrix is a prerequisite for their migration towards the epidermis. To this end, we investigated adhesion of CD34DCs and MoDCs to components of the cutaneous extracellular matrix. Distinct DC subsets showed a differential binding pattern to proteins of the extracellular matrix. MoDCs and CD34DCs bound preferentially to laminin 332 via CD49f and to fibronectin via CD49e, but only weakly to laminin 111 or to collagens. While CD14(pos) cells preferentially bound to laminin 332, CD1a(pos) cells adhered to fibronectin. In summary, subpopulations of CD34DCs and MoDCs are phenotypically related to each other, but not identical and display differential binding to components of the extracellular matrix.
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PMID:Subpopulations of human dendritic cells display a distinct phenotype and bind differentially to proteins of the extracellular matrix. 1768 29


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