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 probably are required for the migration of T lymphocytes to inflamed tissues, but the roles of these molecules have yet to be understood in the pathogenesis of inflammatory diseases such as multiple sclerosis. The adhesion of an SJL murine T cell clone specific for myelin basic protein (MBP) to endothelial cells (ECs) from SJL newborn brain microvessels was examined. Sixty percent of the 2 x 10(4) T cell clones stimulated once every 2 weeks with MBP were bound to ECs, whereas less than 5% of the same number of lymphocytes from peripheral lymph nodes were bound. However, binding was not central nervous system (CNS)-specific. Monoclonal antibody to VLA-4 or VCAM-1 partially inhibited the binding of the T cell clone to ECs. Binding of the T cell clone to ECs increased when the latter were incubated with IL-1 or TNF, but was not inhibited by anti-VLA-4 or VCAM-1. We suggest that the VLA-4/VCAM-1 pathway functions in the binding of the T cell clone specific for MBP to brain ECs but that adhesion molecules other than VLA-4/VCAM-1 are involved because anti-VLA-4 and anti-VCAM-1 did not produce complete inhibition.
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PMID:Binding of an SJL T cell clone specific for myelin basic protein to SJL brain microvessel endothelial cells is inhibited by anti-VLA-4 or its ligand, anti-vascular cell adhesion molecule 1 antibody. 768 92

Fronto-ethmoidal mucocoeles have the capacity to destroy bone. Sinus lining tissue has been obtained at surgery from patients with mucocoeles, from those with chronic sinusitis undergoing endoscopic sinus surgery and from patients undergoing craniofacial resection. Tissues have been frozen, sectioned, and subjected to immunohistochemical examination with monospecific antibodies for the presence of the potent osteolytic cytokines interleukins-1 and -6 and tumour necrosis factor alpha. In addition, the chemotactic intercrine--interleukin-8 was investigated. The presence of the cytokine-inducible vascular endothelial adhesion receptors--Inter-Cellular Adhesion Molecule (ICAM)-1 and E-Selectin (also known as Endothelial Leukocyte Adhesion Molecule--ELAM) was also determined. Normal sinus tissue showed no immunoreactivity with the antibodies to these various moieties. Surprisingly, only a small proportion of tissues from patients with chronic sinusitis showed the presence of cytokines or vascular adhesion receptors. In contrast, all specimens of fronto-ethmoidal mucocoeles showed positive staining for IL-1 alpha and beta and for ICAM-1 and E-selectin. IL-1 immunostaining was restricted to the epithelial cell population not being found in infiltrating leukocytes. In 40% of mucocoeles infiltrating macrophage-like cells showed the presence of tumour necrosis factor alpha. The presence of the potent osteolytic cytokine--IL-1 in all specimens of fronto-ethmoidal mucocoeles coupled to the finding of the IL-1-inducible adhesion molecules ICAM-1 and E-Selectin argues strongly that IL-1 is released from the epithelial cells and that this cytokine may be the factor causing the erosion of bone overlying the expanding mucocoele. The nature of the signals inducing cytokine synthesis remain, however, unidentified.
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PMID:Involvement of cytokines and vascular adhesion receptors in the pathology of fronto-ethmoidal mucocoeles. 769 Oct 23

Microvascular endothelial cells (EC) recruit circulating leukocytes at sites of inflammation, in part through cytokine-regulated expression of endothelial-leukocyte adhesion molecules. Adhesion molecule expression varies among vascular beds and among EC within microvessels of a particular vascular bed. In the present study, we have examined the patterns of antigen expression and cytokine responsiveness of dermal microvascular endothelial cells (DMEC) in a skin organ culture model and, for comparison, in cell culture. Within the superficial vascular plexus (SVP) of normal skin, CD36 molecule expression is undetectable on capillary loops and is expressed on DMEC in only 20% of the larger, horizontal vessels. CD36 expression is not modulated by cytokines. Endothelial-leukocyte adhesion molecule-1 (ELAM-1) expression induced at 6 and 24 h by TNF or IL-1, is restricted to the venular side of the capillary loop and to the venules proper. Vascular cell adhesion molecule-1 (VCAM-1) expression is not inducible on EC of the SVP in normal skin by TNF, IL-1, or IL-4, alone or in combination at either time point. When inflamed skin is examined in organ culture, SVP EC are cytokine responsive regarding VCAM-1 expression. Within the deep vascular plexus (DVP). CD36 molecules are expressed on EC in all capillaries and small vessels. Both ELAM-1 and, to a lesser extent, VCAM-1 expression are inducible by TNF, IL-1, and/or IL-4 on capillaries and larger microvessels at 6 and 24 h. The larger vessels at the dermal-subcutaneous border were found to be CD36-/ELAM-1+/VCAM-1+ after cytokine treatment. CD36 expression of DMEC in cell culture varies from 47 to 98% of cells (mean 75%) in seven separate isolates and is not modified by cytokines. Upon TNF or IL-1 activation, 50 to 90% of DMEC express ELAM-1 molecules at 6 h and expression persists at high levels for 24 h. VCAM-1 expression is negligible at both times. These results with DMEC differ from human umbilical vein EC analyzed in parallel, which are completely CD36- and show transient ELAM-1 and sustained VCAM-1 expression in response to TNF and IL-1. In summary, we have demonstrated that DMEC comprise a heterogeneous population that differ from umbilical vein EC.
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PMID:Heterogeneity of dermal microvascular endothelial cell antigen expression and cytokine responsiveness in situ and in cell culture. 769 64

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 presence and upregulation of adhesion molecules on bovine brain endothelial cells (BBEC) were investigated. Monolayers of BBEC were incubated with lipopolysaccharide (LPS), interleukin-1 beta (rhIL-1 beta), and interleukin-6 (rhIL-6) to simulate in vitro an inflammatory site in the cerebral capillaries. Adhesion of lymphocytes to BBEC increased 4.1-fold after stimulation of the endothelial cells for 4 h with 5 or 10 ng/ml LPS. Lymphocyte adhesion increased after incubation of the BBEC for 4 h with IL-1 and was increased 3.7-fold using 100 ng/ml IL-1. BBEC pre-incubated with IL-6 for 4 h also showed an increase in adhesion of lymphocytes, and cells pretreated with 100 ng/ml IL-6 showed a 3-fold increase in lymphocyte adherence. Specific monoclonal antibodies directed against CD11a, CD18, and VLA-4 were able to block adherence of lymphocytes to stimulated BBEC. These results indicate that the in vitro activation of BBEC may serve as a model for the study of inflammation of the blood-brain barrier.
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PMID:Lymphocyte adhesion to brain capillary endothelial cells in vitro. 791 76

Adhesive interactions between lymphocytes and components of the extracellular matrix (ECM) within a wound environment play a crucial role in determining the inflammatory response following tissue injury. In fetal wounds the extracellular matrix is composed predominantly of hyaluronic acid. Within this environment the inflammatory reaction as a result of injury is minimal. We propose that this lack of an inflammatory cell response in the fetal wound is due to the high levels of hyaluronic acid within the ECM and the inability of lymphocytes to adhere to this matrix component. Therefore, we examined the adhesive properties of fetal lymphocytes to fibronectin, vitronectin, collagen types I, III, IV, V, and hyaluronic acid--ECM components involved in fetal and adult wound environments. Fetal lymphocytes from both spleen and thymus demonstrated significant binding capabilities to fibronectin, vitronectin, and collagen types I and III. No intrinsic binding capabilities were detected to hyaluronic acid. Adhesion was not affected by the addition of IL-1, IFN-gamma, or phorbol dibutyrate. The inability of lymphocytes to adhere to hyaluronic acid helps to explain the lack of inflammation found in fetal wounds and serves to demonstrate the importance of ECM-lymphocyte interactions in determining the inflammatory response during fetal wound healing.
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PMID:The extracellular matrix of the fetal wound: hyaluronic acid controls lymphocyte adhesion. 804 Nov 33

Microvascular endothelial cells derived from the blood-retinal barrier were grown in vitro and various factors affecting the adhesion of syngeneic lymphocytes to these monolayers was evaluated. Under resting conditions 5.3 +/- 0.4% of lymphocytes derived from peripheral lymph nodes (PLN) were found to adhere to the endothelia. Adhesion of resting lymphocytes increased significantly following endothelial treatment with interferon-gamma (IFN-gamma; 11.7 +/- 1.0%), interleukin-1 (IL-1; 14.9 +/- 1.2%), astrocyte conditioned medium (ACM; 12.7 +/- 0.9%) or forskolin (13.9 +/- 1.2%). Lymphocyte activation with concanavalin A (ConA) increased adhesion to 17.0 +/- 0.9% which could be augmented by activating the endothelia with IFN-gamma (22.3 +/- 1.0%), IL-1 (24.0 +/- 1.0%) and ACM (25.7 +/- 1.6%). An antigen-specific CD4+ T cell line exhibited the greatest degree of adhesion, 40.4 +/- 2.5% on resting endothelia, 60.0 +/- 3.0% on IFN-gamma-activated cells and 54.3 +/- 1.4% on IL-1-activated cells. Although CD4+ lymphocytes predominated in the PLN population by 2:1, significantly more CD8+ cells were found to adhere.
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PMID:Lymphocyte adhesion to cultured endothelial cells of the blood-retinal barrier. 822 14

The adhesion of leukocytes to the endothelium is a hallmark in the development of an inflammation. Adhesion is caused by a number of mechanisms that depend upon the activation of the endothelium. The adhesion has to be specific for the different leukocyte types. I review here recent data with respect to polymorphonuclear granulocytes (PMN) adhesion to the endothelium of an inflammatory site. I especially focus on the pivotal role of Interferon gamma in the regulation of PMN adhesion to the endothelium. It modulates the adhesion of PMN caused by activation by other cytokines like IL-1, but does not affect the cell surface expression of the known adhesion molecules. I postulate the existence of a new class of cell surface modulators of adhesion which participate in the multiple step process of cell-cell adhesion.
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PMID:Complex regulation of granulocyte adhesion to cytokine-activated endothelium. 825 Aug 7

The pathophysiology of vaso-occlusive crisis in sickle cell disease involves interactions among blood cells, plasma proteins, and vessel wall components. The initial goal of this work was to quantify the adhesion of sickle red blood cells (RBCs) to fibronectin immobilized on glass under both static and dynamic shear stress conditions. High-power microscopic inspection of static assay plates showed striking numbers of adherent neutrophils as well as RBCs. Sickle neutrophils and RBCs were significantly more adherent to fibronectin than the corresponding normal cells in static adhesion assays. Adhesion of both sickle neutrophils and sickle RBCs in dynamic adhesion assays was promoted by a period of static incubation preceding initiation of shear stress conditions. Adherent neutrophils remained attached at shear stresses up to 51 dyne/cm2; most adherent RBCs were attached at shear stresses up to 13 dyne/cm2, but detached at a shear stress of 20 dyne/cm2. Sickle neutrophil adhesion was enhanced significantly by autologous plasma. Elevated levels of plasma interleukin-6 (IL-6; but not IL-1 or IL-8) were found in 6 of 9 sickle cell disease samples examined, and elevated levels of tumor necrosis factor were found in 2 of 9 samples. Plasma IL-6 levels correlated positively with both the number of sickle neutrophils adherent to fibronectin and the ability of sickle plasma to enhance adhesion of normal neutrophils to fibronectin. These data suggest possible roles for neutrophil activation and for fibronectin in mediating sickle neutrophil and RBC adhesion.
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PMID:Adhesion of sickle neutrophils and erythrocytes to fibronectin. 855 2

Dietary balance of long-chain fatty acids (FA) may influence human susceptibility to pathological processes which involve the interaction of leukocytes with vascular endothelium, such as atherogenesis and inflammation. Such interaction is largely mediated by the de novo or increased expression of endothelial leukocyte adhesion molecules on vascular endothelial cells, able to tether and stably bind leukocytes onto the vessel wall, and by the production of leukocyte chemoattractants. Endothelial cells do not normally support high levels of leukocyte adhesion. They do so, however, when exposed to a number of stimuli, such as oxidized low density lipoprotein bacterial lipopolysaccharides, and inflammatory cytokines, which induce phenotypic changes generally referred to as "endothelial activation." We compared various FA in their ability to modulate endothelial activation by cytokines. FA included linoleic, arachidonic, oleic, eicosapentaenoic and, docosa-hexaenoic acid (DHA) as representatives of the n-6, n-3 polyunsaturated FA and of the monounsaturated FA. The n-3 FA DHA, and, to a lesser extent, oleate, at nutritionally compatible concentrations, were able to reduce endothelial expression of Vascular Cell and Adhesion Molecule-1 (VCAM-1). In further studies, DHA dose- and time-dependently reduced also the expression of E-selectin, Intercellular Adhesion Molecule-1, interleukin (IL)-6 and IL-8, in response to IL-1, IL-4, tumor-necrosis factor, or bacterial endotoxin. The magnitude of this effect paralleled its incorporation into cellular phospholipids. Also, coordinate with reduced surface adhesion molecule expression, DHA reduced the adhesion of human monocytes and of monocytic U937 cells to cytokine-stimulated endothelial cells. These effects were accompanied by a quantitatively consistent reduction in VCAM-1 mRNA, indicating a pretranslational control of adhesion molecule gene expression. These novel properties of FA as modulators of endothelial activation may help to explain the influence of dietary FA intake on atherogenesis and inflammation.
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PMID:Control of endothelial leukocyte adhesion molecules by fatty acids. 872 95


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