UMLS:C0001511 - FACTA Search

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Query: UMLS:C0001511 (Adhesion)
5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Early in inflammation, adhesion occurs between leukocytes and endothelium when selectins bind to sialyl Lewis X (sLex) and related oligosaccharides. We tested novel compounds that mimic sLex for their ability to inhibit selectin-mediated adhesion of human eosinophils and neutrophils in vitro. Neutrophils and eosinophils were isolated by density gradient centrifugation, and eosinophils were further purified by immunomagnetic negative selection. Adhesion to unstimulated or interleukin-1beta-stimulated (5 ng/ml, 4-6 h) umbilical vein endothelial monolayers was tested under static or rotating conditions, where adhesion is primarily E- or L-selectin dependent, respectively. P-selectin-dependent adhesion was tested on immobilized platelets treated with or without phorbol myristate acetate (10(-7) M, 10 min). Stimulus-induced adhesion was always at least 4-fold higher than without stimulus, and selectin dependence was confirmed with specific blocking monoclonal antibodies. E-selectin-dependent adhesion of eosinophils and neutrophils was inhibited by compound GM2296 (the concentration producing 50% inhibition of adhesion [IC50] approximately 0.5-1 mM). E-selectin-dependent adhesion of neutrophils, but not eosinophils, was also inhibited by another compound, sLex with a lipid tail (30 +/- 6% inhibition at 3 mM), whereas compound GM1292 slightly inhibited adhesion of both (23 +/- 5 and 20 +/- 6% inhibition, respectively, at 1 mM). L-selectin-dependent adhesion was more effectively inhibited by GM2296 (IC50 approximately 0.2-0.5 mM), although P-selectin-dependent adhesion was also inhibited (IC50 approximately 1 mM). Inhibition was reversible without affecting viability, and no effect was seen with these compounds in assays testing neutrophil adhesion to immobilized intercellular adhesion molecule-1. Thus, compound GM2296, a carbon-fucosylated derivative of glycyrrhetinic acid, inhibits E-, L-, and P-selectin-dependent eosinophil and neutrophil adhesion. The ability of these and perhaps other related glycomimetic compounds to interfere with the function of more than one type of selectin makes them desirable candidates as anti-inflammatory agents.
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PMID:Antagonism of selectin-dependent adhesion of human eosinophils and neutrophils by glycomimetics and oligosaccharide compounds. 980 49

While CD4 and several chemokine receptors are the principal receptors for human immunodeficiency virus type 1 (HIV-1) viruses, other cell membrane proteins also play a role in HIV-1 infection. A large array of host cell-derived membrane proteins, including adhesion molecules, are incorporated into the envelope of HIV-1 virions, and the profile of host cell proteins acquired by the virus depends on the cells used to propagate the virus. The major leukocyte adhesion molecules, such as leukocyte-function associated antigen-1 (LFA-1), intercellular adhesion molecule-1 (ICAM-1), and CD44, retain their biological functions when expressed on the virion surface, and have been shown to increase virus-cell interaction, enhance virus infectivity, and extend the host cell range of the virus. LFA-1 and its ICAM ligands are also necessary for syncytium formation and cell-to-cell transmission of HIV-1. Furthermore, several studies demonstrate that the presence and level of cell-derived adhesion molecules on the surface of HIV-1 virions affect the process by which antibody-mediated virus neutralization occurs and is measured: the level of virus neutralization is influenced by the host cell-derived adhesion molecules present on the virus, and thus, by the type of host cells in which the virus was produced. Adhesion molecules expressed on the target cells used in neutralization assays similarly affect HIV-1 neutralization by virus-specific antibodies. Consistent with these observations is the finding that neutralizing activities of both HIV+ plasma and human anti-gp120 monoclonal antibodies (Mabs) are enhanced by an anti-LFA-1 Mab capable of blocking LFA-1 functions. Hence, LFA-1, ICAM-1, and other cellular adhesion molecules are involved in different stages of HIV-1 infection and profoundly affect HIV-1 neutralization by virus-specific antibodies. These findings illuminate the biology of virus-cell interactions and have significant implications for evaluating candidate HIV vaccines.
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PMID:Role of cellular adhesion molecules in HIV type 1 infection and their impact on virus neutralization. 981 51

Adhesion molecules are known to play a crucial role in the recruitment of inflammatory cells to sites of inflammation. In this study endothelial cell and keratinocyte adhesion molecule expression in recurrent oral ulcers (ROU) (n = 13) was compared with that found in normal oral mucosa (NOM) (n = 11) and experimentally induced ulcers (EIU) (n = 5) by using immunohistochemistry. Significantly greater expression of both vascular cell adhesion molecule- (VCAM-1) and E-selectin was demonstrated on vasculature in ROU compared with that found in both NOM and EIU. Induction of keratinocyte intercellular adhesion molecule-1 (ICAM-1) was also a prominent feature of ROU. The expression of VCAM-1 and E-selectin on blood vessels in ROU is likely to be important in the accumulation of lymphocytes that characterise early aphthous lesions. The induction of keratinocyte ICAM-1 may facilitate lymphocyte invasion of the epithelium in ROU, which may ultimately result in ulcer formation.
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PMID:Induction of adhesion molecule expression on blood vessels and keratinocytes in recurrent oral ulceration. 989 Apr 50

Because oleic acid is implicated in the antiatherogenic effects attributed to the Mediterranean diet, we investigated whether this fatty acid can modulate endothelial activation, ie, the concerted expression of gene products involved in leukocyte recruitment and early atherogenesis. We incubated sodium oleate with human umbilical vein endothelial cells for 0 to 72 hours, followed by coincubation of oleate with human recombinant tumor necrosis factor, interleukin (IL)-1alpha, IL-1beta, IL-4, Escherichia coli lipopolysaccharide (LPS), or phorbol 12-myristate 13-acetate for a further 6 to 24 hours. The endothelial expression of vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and intercellular adhesion molecule-1 was monitored by cell surface enzyme immunoassays or flow cytometry, and steady-state levels of VCAM-1 mRNA were assessed by Northern blot analysis. At 10 to 100 micromol/L for >24 hours, oleate inhibited the expression of all adhesion molecules tested. After a 72-hour incubation with oleate and a further 16-hour incubation with oleate plus 1 microg/mL LPS, VCAM-1 expression was reduced by >40% compared with control. Adhesion of monocytoid U937 cells to LPS-treated endothelial cells was reduced concomitantly. Oleate also produced a quantitatively similar reduction of VCAM-1 mRNA levels on Northern blot analysis and inhibited nuclear factor-kappaB activation on electrophoretic mobility shift assays. Incubation of endothelial cells with oleate for 72 hours decreased the relative proportions of saturated (palmitic and stearic) acids in total cell lipids and increased the proportions of oleate in total cell lipids without significantly changing the relative proportions of polyunsaturated fatty acids. Although less potent than polyunsaturated fatty acids in inhibiting endothelial activation, oleic acid may contribute to the prevention of atherogenesis through selective displacement of saturated fatty acids in cell membrane phospholipids and a consequent modulation of gene expression for molecules involved in monocyte recruitment.
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PMID:Oleic acid inhibits endothelial activation : A direct vascular antiatherogenic mechanism of a nutritional component in the mediterranean diet. 997 1

Adhesions of leukocytes to hepatocytes and sinusoidal endothelial cells mediates the induction and progression of hepatic injury. However, in contrast to endothelial cells, information regarding the regulation of interactions between leukocytes and hepatocytes is limited. In the present study, we investigated the effect of inflammatory mediators including lipopolysaccharide (LPS), staphylococcal enterotoxin B (SEB), interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta) on the adhesion of polymorphonuclear leukocytes or lymphocytes to primary cultured rat hepatocytes, and on the expression of intercellular adhesion molecule-1 (ICAM-1) gene in hepatocytes. Both polymorphonuclear leukocyte and lymphocyte adhesion to hepatocytes were enhanced after exposure of hepatocytes to IFN-gamma and TNF-alpha, but not after exposure to LPS, SEB or IL-1beta. The adhesion induced by either IFN-gamma or TNF-alpha was inhibited by monoclonal antibodies against ICAM-1 or lymphocyte function-associated antigen-1 (LFA-1). Nonstimulated hepatocytes expressed faintly ICAM-1 mRNA, which increased slightly during the culture period. ICAM-1 mRNA expression was up-regulated to a greater extent by incubating hepatocytes with IFN-gamma or TNF-alpha, and peaked after 12 hr of incubation with TNF-alpha and after 24 hr with IFN-gamma. These results indicate that IFN-gamma and TNF-alpha induce the expression of ICAM-1 on parenchymal hepatocytes and that the LFA-1-ICAM-1 pathway plays an important role in the interaction between hepatocytes and neutrophils or lymphocytes.
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PMID:Effects of cytokines on the binding of leukocytes to cultured rat hepatocytes and on the expression of ICAM-1 by hepatocytes. 1021 41

Mobilization of nuclear factor-kappaB (NF-kappaB) activates transcription of genes encoding endothelial adhesion molecules and chemokines that contribute to monocyte infiltration critical in atherogenesis. Inhibition of NF-kappaB has been achieved by pharmacological and genetic approaches; however, monocyte interactions with activated endothelium in shear flow following gene transfer of the NF-kappaB inhibitor IkappaB-alpha have not been studied. We found that overexpression of IkappaB-alpha in endothelial cells using a recombinant adenovirus prevented tumor necrosis factor-alpha (TNF-alpha)-induced degradation of IkappaB-alpha and suppressed the upregulation of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin mRNA and surface protein expression and the upregulation of transcripts for the chemokines monocyte chemoattractant protein 1 (MCP-1) and growth-related activity-alpha (GRO-alpha) by TNF-alpha. This was associated with a reduction in endothelial MCP-1 secretion and GRO-alpha immobilization. Adhesion assays under physiological shear flow conditions showed that firm arrest, spreading, and transmigration of monocytes on TNF-alpha-activated endothelium was markedly inhibited by IkappaB-alpha overexpression. Inhibition with monoclonal antibodies and peptide antagonists inferred that this was due to reduced expression of Ig integrin ligand as well as of chemokines specifically involved in these events. In contrast, rolling of monocytes was increased by IkappaB-alpha transfer and was partly mediated by P-selectin; however, it appeared to be unaffected by the inhibition of E-selectin induction. Thus, our data provide novel evidence that selective modulation of NF-kappaB by adenoviral transfer of IkappaB-alpha impairs the expression of multiple endothelial gene products required for subsequent monocyte arrest and emigration in shear flow and thus for monocyte infiltration in atherosclerotic plaques.
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PMID:Monocyte arrest and transmigration on inflamed endothelium in shear flow is inhibited by adenovirus-mediated gene transfer of IkappaB-alpha. 1033 75

Adhesion molecules on the endothelial surface of the blood-brain barrier (BBB) play an important role in the pathogenesis of many encephalopathies, including multiple sclerosis (MS) and cerebral malaria (CM). The expression of four surface molecules of relevance to MS and CM on the immortalized human umbilical vein endothelial cell line, ECV304, was investigated using immunofluorescence flow cytometry. We found that ECV304 cells express intercellular adhesion molecule-1 (ICAM-1) and low levels of CD36, but not vascular cell adhesion molecule-1 (VCAM-1) or E-selectin. This expression pattern was unaltered on ECV304 cells which were co-cultured with C6 glioma cells; conditions under which the endothelial cells display enhanced barrier formation. Tumour necrosis factor-alpha (TNF-alpha), which is elevated in MS and CM, decreased the integrity of the barrier in co-cultured endothelial cells and upregulated the expression of ICAM-1 nine-fold. The significance of elevated ICAM-1 expression in relation to the binding of parasitised erythrocytes at the BBB in CM is discussed.
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PMID:Upregulation of intercellular adhesion molecule-1 expression on human endothelial cells by tumour necrosis factor-alpha in an in vitro model of the blood-brain barrier. 1036 90

Polymorphonuclear leukocytes (PMN) and eosinophils (Eos) are important cellular participants in a variety of acute and chronic inflammatory reactions in the airway. Histologic evidence has implicated direct interactions between these two subsets of leukocytes and airway epithelial cells during inflammation. A comprehensive characterization and comparison of physiologic stimuli and adhesion molecule involvement in granulocyte-epithelial-cell interactions done with nontransformed human airway epithelial cells has not been reported. We therefore examined the regulation and biochemical mechanisms governing granulocyte-epithelial-cell adhesion, using either purified PMN or Eos and primary cultures of human bronchial epithelial cells (HBECs). We investigated the involvement of a number of proinflammatory signals associated with allergic and nonallergic airway inflammation, as well as the contribution of several epithelial and leukocyte adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and members of the beta(1), beta(2), and beta(7) integrin families. ICAM-1 was expressed at low levels on cultured HBECs and was markedly upregulated after stimulation with interferon (IFN)-gamma or, to a lesser extent, with tumor necrosis factor (TNF)-alpha or interleukin (IL)-1. VCAM-1 was not present on resting HBECs, and was not upregulated after stimulation with IFN-gamma, IL-1, IL-4, or TNF-alpha. PMN adhesion to HBECs could be induced either through activation of PMN with IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF), or C5a, but not with IL-5 or by preactivation of HBECs with TNF-alpha or IFN-gamma. Blocking antibody studies indicated that PMN-HBEC adherence depended on beta(2) integrins, primarily alpha(M)beta(2) (Mac-1). Adherence of Eos to HBECs could be induced through activation of Eos with IL-5, GM-CSF, or C5a, but not with IL-8 or by prior activation of HBECs with TNF-alpha of IFN-gamma. Maximal adhesion of Eos and PMN required pretreatment of HBECs with either TNF-alpha or IFN-gamma in addition to leukocyte activation. Adherence of Eos to unstimulated HBECs was mediated through both beta(1) and beta(2) integrins, whereas adhesion of Eos to activated HBECs was dominated by beta(2) integrins. Adhesion of both Eos and PMN was inhibited by treatment of HBECs with blocking antibodies to ICAM-1. Differential utilization of beta(1) and beta(2) integrins by Eos, depending on the activation state of the epithelium, is a novel finding and may affect activation and/or recruitment of Eos in airway tissue. Mechanisms of adhesion of HBECs to Eos and PMN, as evidenced by the different responsiveness of the two latter types of cells to IL-8 and IL-5, may account for a prevalence of Eos over PMN in certain airway diseases.
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PMID:Mechanisms and regulation of polymorphonuclear leukocyte and eosinophil adherence to human airway epithelial cells. 1046 Jul 60

Intraepithelial lymphocytes (IEL) utilize the integrin alphaebeta7 on their surface to bind to E-cadherin on epithelial cells in the gut and breast. In oral mucosa and skin IEL express alphaebeta7 and the cutaneous lymphocyte-associated antigen (CLA) but the mechanisms of adhesion of these subsets to keratinocytes are unknown. Levels of alphaebeta7 and CLA were up-regulated on peripheral blood lymphocytes (PBL) by transforming growth factor-beta (TGF-beta) and interleukin-12 (IL-12), respectively, and both groups of lymphocytes adhered onto oral and skin keratinocytes. Adhesion of IL-12-activated PBL was totally abolished by anti-lymphocyte-associated function antigen type 1 (anti-LFA-1) antibodies but was unaffected by anti-alphaebeta7 antibodies indicating that adhesion of the CLA-positive subset is mediated via LFA-1 interaction with intercellular adhesion molecule-1 (ICAM-1). Adhesion of TGF-beta-activated PBL to E-cadherin-positive oral and skin keratinocytes was partially inhibited by anti-alphaebeta7 antibodies but was unaffected by the blocking antibody E4.6 against E-cadherin which detects the binding site for alphaebeta7-positive lymphocytes in breast and gut epithelium. TGF-beta-activated PBL also bound to an E-cadherin-negative oral keratinocyte cell line and adhesion was inhibited by anti-alphaebeta7 antibodies. These results strongly suggest that in oral epithelium and epidermis alphaebeta7-positive lymphocytes do not bind to E-cadherin and there may be a novel second ligand for the alphaebeta7 integrin.
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PMID:Mechanisms of binding of cutaneous lymphocyte-associated antigen-positive and alphaebeta7-positive lymphocytes to oral and skin keratinocytes. 1046 28

The development of atherosclerosis is accelerated in individuals with type 2 diabetes. Adhesion of monocytes to the vascular endothelium is a key initial step in atherogenesis. We have previously shown that monocyte adhesion to human aortic endothelial cells (HAECs) cultured long-term in high-glucose medium (25 mmol/L, 2 passages) is increased compared with cells grown in normal glucose (5 mmol/L). One potential mechanism for increased monocyte adhesion to HAECs under hyperglycemic conditions is via the 12-lipoxygenase (12-LO) pathway. In this study, we demonstrated in HAECs that the major LO metabolite of arachidonic acid was the 12-LO product, 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE], which was increased severalfold in HAECs cultured under high-glucose conditions. Furthermore, treatment of HAECs with 12(S)-HETE induced monocyte, but not neutrophil, adhesion an average of 3-fold (range of 1.5- to 5-fold) compared with untreated cells (75+/-5 versus 26+/-1 monocytes per field, respectively, P<0.001). Expression of the adhesion molecules vascular cell adhesion molecule-1, E-selectin, and intercellular adhesion molecule-1 was not significantly increased. However, both glucose and 12(S)-HETE induced a 60% increase in HAEC surface expression of connecting segment-1 (ie, CS-1) fibronectin, a ligand for very late-acting antigen-4 (VLA-4). The antibodies used to block monocyte integrin VLA-4 and leukocyte function-related antigen-1, a monocytic counterreceptor for intercellular adhesion molecule-1, inhibited the ability of both 12-LO products and high glucose to induce monocyte adhesion. These results definitively demonstrate for the first time in HAECs that the 12-LO pathway can induce monocyte-endothelial cell interaction and that the effects of glucose may be mediated, at least in part, through this pathway. Thus, these results suggest that the 12-LO pathway may play a role in the increased susceptibility of diabetics to atherosclerosis.
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PMID:Lipoxygenase products increase monocyte adhesion to human aortic endothelial cells. 1055 3

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