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)

Adhesion molecules recently have been considered to play an important role in inflammatory processes in bronchial asthma. Our previous study revealed high expression of beta 2-integrin family (CR3, LFA-1 alpha, CD18) on hypodense eosinophils. Thus, from the point of view of cell-to-cell interaction between mononuclear cells and eosinophils, we examined whether the supernatant of mononuclear cells obtained from mite-allergic asthmatic patients cultured with specific allergen mite-allergen is involved in adhesion molecule expression using an eosinophilic cell line (EoL-1). These characteristics of beta 2-integrin family expression (high expression of beta 2 integrin) were induced by the supernatant of mononuclear cells from mite-allergic asthmatic patients stimulated with mite-allergen as well as with a combination of the recombinant eosinophilopoietic growth cytokines (IL-3, GM-CSF and IL-5). Thus, we could conclude that some cytokines produced by specific allergen stimulated mononuclear cells in asthmatics might be involved in allergic inflammation through the induction of adhesion molecule expression on eosinophils in asthma or allergic disorders.
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PMID:Induction of beta 2 integrin expression on an eosinophilic cell line (EoL-1) by the supernatant of mononuclear cells stimulated with specific allergen from asthmatic patients. 782 26

Adhesion of circulating cells to vascular endothelium occurs in the early phase of inflammation, and is mediated by specific cell adhesion molecules. Many such adhesion molecules are increased in inflamed regions of ulcerative colitis (UC) and Crohn's disease (CD) but there is limited knowledge of their expression in the uninvolved gut, adjacent to inflammation. We investigated immunohistochemically the expression of platelet endothelial cell adhesion molecule-1 (PECAM-1), intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) on resected specimens taken at a distance of 2-4 cm from the inflamed area and without histological signs of inflammation. Compared with normal gut, we found (i) a significant increase of PECAM-1-positive vessels in the mucosa of uninvolved UC (149.0 +/- 24.1 vessels/mm2 (mean +/- s.d.); normal colon = 123.1 +/- 21.6; P = 0.004); (ii) a significant decrease of ICAM-1-positive vessels in uninvolved CD (111.9 +/- 22.6 vessels/mm2; normal ileum = 136.9 +/- 27.6; P = 0.04); and (iii) a moderate but statistically insignificant increase of LFA-1-positive cells in the mucosa of uninvolved UC and Crohn's ileitis. This altered expression of cell adhesion molecules may contribute to the early lesion in inflammatory bowel disease and provide new therapeutic opportunities.
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PMID:Altered expression of cell adhesion molecules in uninvolved gut in inflammatory bowel disease. 790 Sep 41

Adhesion molecules play a critical role in leukocyte emigration to a site of inflammation. In order to assess the potential therapeutic benefit of blocking adhesion molecule function in anterior uveitis, the efficacy of antibodies to specific adhesion molecules was tested in 3 separate rabbit models of anterior uveitis. Antibodies to two different leukocyte molecules, CD11a and CD18, and antibodies to the endothelial ligand for CD11a/CD18, ICAM-1 (intercellular adhesion molecule-1, CD54), were studied in inflammation after intravitreally injected interleukin-1, intravitreally injected endotoxin, or an ocular reversed passive Arthus reaction. The CD18 antibody (2 mg/kg intravenously) reduced the cellular infiltrate with each of these 3 models. The antibody to CD11a was equally effective but was tested only in the IL-1-induced model. The antibody to ICAM-1 reduced the cellular infiltrate associated with this model, but the results did not reach statistical significance. None of the antibodies was able to reduce the associated increase in vascular permeability as measured by protein in the aqueous humor. The antibody to CD18 failed to reduce the inflammation if it was administered 24 hours after the intravitreally injected endotoxin. These observations demonstrate that leukocyte migration into the anterior segment of the eye is dependent on the CD11a/CD18 complex.
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PMID:Efficacy of antibodies to adhesion molecules, CD11a or CD18, in rabbit models of uveitis. 790 35

The intercellular adhesion of circulating leukocytes to vascular endothelium is a prerequisite for leukocyte emigration from the blood to extravascular tissues. This process is facilitated by adhesion molecules on the surfaces of both the vascular endothelial cells and the leukocytes. The experiments presented here demonstrate for the first time that the leukocyte adhesion receptor, intercellular adhesion molecule-1, is constitutively expressed on cultured cerebromicrovascular endothelial cell lines derived from both spontaneously hypertensive (SHR) rats and normotensive Wistar-Kyoto (WKY) rats. Both cultures contained similar numbers of cells constitutively expressing this adhesion molecule (31.4% and 29.6%, respectively). Adhesion molecule expression was up-regulated by interleukin-1 beta, tumor necrosis factor-alpha, interferon-gamma and lipopolysaccharide in a dose- and time-dependent manner. Both cultures exhibited similar maximum levels of adhesion molecule up-regulation to optimal concentrations of all three cytokines. However, SHR endothelial cells were more sensitive to all three cytokines; significantly higher levels of intercellular adhesion molecule-1 expression were seen on SHR as opposed to WKY endothelial cells cultured with sub-optimal cytokine concentrations. It was also observed that lipopolysaccharide up-regulated intercellular adhesion molecule-1 expression on SHR endothelial cells to a greater extent than on WKY endothelial cells. The findings that intercellular adhesion molecule-1 can be up-regulated to a greater degree on SHR endothelial cells may have important implications for in vivo perivascular leukocyte accumulation under hypertensive conditions. These observations indicate a possible mechanism by which hypertension may predispose to the development of disorders such as atherosclerosis and stroke.
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PMID:Adhesion molecules on normotensive and hypertensive rat brain endothelial cells. 790 12

Neutrophils and monocytes (phagocytes) are important mediators of injury in many inflammatory diseases, including glomerulonephritis and vasculitis. Current treatment modalities (eg, corticosteroids, cytotoxic agents) are relatively nonspecific in their actions, frequently ineffective, and often associated with immunologic or metabolic complications. Recent advances in cellular and molecular immunobiology have suggested novel targets for therapeutic intervention. Phagocyte adhesion to endothelial cells, in particular, is a central event in the recruitment of phagocytes to sites of inflammation. Phagocyte trafficking to the extravascular space requires the coordinated interactions of several families of adhesion molecules, including the selectins, integrins, and immunoglobulin-like molecules. Initial attachment appears to be achieved by the interaction of phagocyte or endothelial cell selectins with carbohydrate-containing counter-receptors. These events facilitate immobilization of phagocytes via the interaction of phagocyte integrins with immunoglobulin-like molecules on endothelial cells and diapedesis to the extravascular tissue. Chemoattractants and cytokines regulate adhesion by altering the avidity or surface expression of preformed molecules and by influencing de novo synthesis of adhesion molecules. The intensity and composition of leukocyte infiltrates at sites of inflammation likely reflect the local balance of pro- and anti-inflammatory chemoattractants and cytokines and the profile of adhesion molecules on invading and resident cells. Adhesion may also promote tissue injury by augmenting phagocyte oxidative bursts and lysosomal enzyme release and by facilitating release of these cytotoxic molecules in close proximity to tissue cells. In addition, adhesion may amplify the levels and types of inflammatory mediators within a local milieu by promoting transcellular eicosanoid biosynthesis during cell-cell interaction. Increased adhesion molecule expression has been reported in glomerulonephritis, vasculitis, tubulointerstitial nephritis, transplant rejection, and hemodialysis "first-use" reactions. In addition, leukocyte adhesion may be an important event in the pathophysiology of ischemia-reperfusion injury. Monoclonal antibodies against adhesion molecules confer dramatic protection in several models of renal inflammation. Further studies in this area may yield potent and specific therapies for common renal diseases.
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PMID:Leukocyte adhesion molecules: potential targets for therapeutic intervention in kidney diseases. 792 75

Adhesion molecules on the endothelium and leukocytes are involved in mediating cell-cell adhesion, which is an initial step in the leukocyte migration response. These adhesion molecules, some of which are present constitutively and others that can be up-regulated in response to chemotactic and proinflammatory stimuli, regulate the trafficking of leukocytes across the vascular endothelial barrier. A basic mechanism of interaction between the endothelium and leukocytes involves CD11/CD18 integrins, which bind to members of the immunoglobulin super gene family-intercellular adhesion molecule (ICAM)-1 and ICAM-2. The interaction between CD11/CD18 integrins and ICAM-1 is required for leukocyte migration. The other important adhesive interaction between leukocytes and the endothelium involves binding of selectins to their endothelium carbohydrate counterreceptors on leukocytes. The selectin-mediated binding is involved in leukocyte "rolling," whereas CD11/CD18 integrins are responsible for strengthening and stabilizing the leukocyte adhesion. This review summarizes the current literature on leukocyte adhesion molecules, in particular, the endothelial cell interactions mediated by the CD11/CD18 integrins.
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PMID:Endothelial cell interactions and integrins. 792 92

It is now clear that adhesive interactions play a critical role in the process of metastatic tumor dissemination. Adhesion molecules act as both positive and negative modulators of the metastatic process. Molecules such as E-cadherin that promote homotypic tumor cell adhesion function to maintain intercellular contacts that confine cells to the primary tumor site and are negatively correlated with metastatic potential. Because tumor cells are rapidly eliminated from the circulation, those cells that can quickly arrest in the vasculature at a secondary site and pass through the vessel wall into the surrounding tissue will have a selective advantage toward establishing new metastatic colonies. The first step in this process is specific adhesion to venular endothelial cells in selected organs, a process mediated by tumor cell surface molecules such as Sialyl LewisX or the VLA-4 (alpha 4 beta 1) integrin that mediate binding to endothelial adhesion molecules such as the E-selectin or the vascular cell adhesion molecule, VCAM-1. Site-specific endothelial determinants such as the lung endothelial cell adhesion molecule, LuECAM, may additionally specify particular sites for preferential adhesion and subsequent site-specific metastasis of particular tumor types. After adherence to endothelial cells and subsequent endothelial retraction, metastatic tumor cells must adhere to elements of the subendothelial basement membrane such as laminin and types IV and V collagen, interactions frequently mediated by members of the beta 1 and beta 4 integrin families. Finally, metastatic tumor cell adhesion to connective tissue elements such as fibronectin, type I collagen and hyaluronan, mediated by molecules such as the beta 1 integrins and by the CD44 cell surface adhesion molecule, are required for movement of tumor cells into the subendothelial stroma and subsequent growth at these new sites. Thus, metastatic potential can be influenced both positively and negatively by a variety of cell surface adhesive molecules that act both independently and in concert to direct tumor cells to particular tissues, allowing them to arrest in those tissues, migrate across the vessel wall and grow at the secondary site. In the current review, I discuss the nature of the adhesion molecules that have been implicated in the metastatic process, emphasizing those molecules that have been shown to correlate with metastasis in clinical human tumors or that have been shown to influence metastatic potential in in vivo experimental assays.
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PMID:Adhesion molecules in tumor metastasis. 840 Jan 43

One of the genetic components of seropositive rheumatoid arthritis has been mapped to a short sequence stretch in the third hypervariable region of the HLA-DRB1 gene. A new concept has emerged, proposing that the shared-sequence motif is functional in determining the clinical patterns of rheumatoid arthritis and the severity of the disease in a codominant mode. Patients with a double dose of the shared sequence tend to have more serious disease manifestations, suggesting a model in which the genetic element is involved in perpetuating the disease. The pathogenetic model in which the shared epitope selectively binds and presents an arthritogenic peptide appears too simplistic to account for these findings. Our understanding of how the shared epitope may contribute to forming the molecular complex of the T-cell receptor, peptide, and HLA-DR molecule is advancing. Molecular analyses of the synovial T-cell infiltrate continue to define the various components involved in recruiting T cells to the site of synovial inflammation. Adhesion molecules, predominantly the endothelial cell ligands vascular adhesion molecule 1 and endothelial leukocyte adhesion molecule 1, attract phenotypically selected T cells with a wide spectrum of specificities. The rheumatoid factor-positive B cells may be important antigen-presenting cells in the joint and may activate T cells with many different specificities. Rheumatoid factor immunoglobulin genes show clear evidence of somatic mutation, indicating a T cell-dependent, antigen-driven process. Thus, multiple factors contribute to the composition of the inflammatory infiltrate and may well modulate the repertoire of T cells recruited to the tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interplay of T lymphocytes and HLA-DR molecules in rheumatoid arthritis. 845 67

Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are autoimmune diseases in which there is loss of cohesion between keratinocytes (acantholysis) and blistering within the epidermis. PV is characterized by acantholysis predominantly between the epidermal basal cells and suprabasal layers, whereas in PF intraepidermal cleavage is higher in the epidermis. Adhesion between keratinocytes is dependent on the function of transmembrane glycoproteins of the cadherin family present in specialized adhesion junctions, the desmosomes. The pathogenesis of acantholysis in pemphigus is uncertain, but the pemphigus autoantibodies bind to epithelial cadherins. We have used monoclonal antibodies to desmosomal components to investigate their distribution in different forms of pemphigus. Our results show that the localization of desmosomal components is abnormal in intact perilesional epidermis, intact epidermis above the blisters in PV and intact epidermis below the blisters in PF. We suggest that autoantibody binding may have a direct effect on the function of specific epithelial cadherins, but will only cause cell separation where the antigen is the principal adhesion molecule.
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PMID:An immunohistological study of desmosomal components in pemphigus. 849 48

Great interest has been shown for the seeding of autologous endothelial cells on prosthetic materials. We investigated the inflammatory and immunogenic properties of xenogeneic tissue before and after seeding with cultured human great saphenous vein endothelial cells in vitro. Adhesion of monocytes to xenogeneic tissue with or without endothelium and the endothelial cell expression of E-selectin, intercellular adhesion molecule 1, vascular adhesion molecule 1, and major histocompatibility complex class II antigens were investigated 1, 3, and 7 days after seeding. Both monocyte adhesion and endothelial adhesion molecule expression were relatively high 1 day after seeding and were significantly lowered after 3 to 7 days. There was no difference between monocyte adhesion and adhesion molecule expression on viable or nonviable xenogeneic tissue. Monocyte adhesion and adhesion molecule expression increased after interleukin-1 beta or interferon-gamma stimulation of the endothelial cells. The results suggest that human endothelial cells exhibit an early proinflammatory and immunogenic activity immediately after seeding. Three and 7 days after seeding, the endothelialized surface is less adhesive for monocytes as compared with nonendothelialized tissue. These findings have implications when cultured or intraoperatively recruited endothelial cells are used clinically.
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PMID:Reduction of monocyte adhesion to xenogenic tissue by endothelialization: an adhesion molecule and time-dependent mechanism. 852 66


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