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)

Treatment of human endothelial cells with cytokines such as interleukin-1, tumor necrosis factor-alpha (TNF-alpha) or interferon-gamma induces the expression of specific leukocyte adhesion molecules on the endothelial cell surface. Interfering with either leukocyte adhesion or adhesion protein upregulation is an important therapeutic target as evidenced by the potent anti-inflammatory actions of neutralizing antibodies to these ligands in various animal models and in patients. In the present study we report that cotreatment of human endothelial cells with certain hydroxyflavones and flavanols blocks cytokine-induced ICAM-1, VCAM-1, and E-selectin expression on human endothelial cells. One of the most potent flavones, apigenin, exhibited a dose- and time-dependent, reversible effect on adhesion protein expression as well as inhibiting adhesion protein upregulation at the transcriptional level. Apigenin also inhibited IL-1 alpha-induced prostaglandin synthesis and TNF-alpha-induced IL-6 and IL-8 production, suggesting that the hydroxyflavones may act as general inhibitors of cytokine-induced gene expression. Although apigenin did not inhibit TNF-alpha-induced nuclear translocation of NF-kappa B(p50(NFKB1)/p65(RelA)) we found this flavonoid did inhibit TNF-alpha induced beta-galactosidase activity in SW480 cells stably transfected with a beta-galactosidase reporter construct driven by four NF-kappa B elements, suggesting an action on NF-kappa B transcriptional activation. Adhesion of leukocytes to cytokine-treated endothelial cells was blocked in endothelial cells cotreated with apigenin. Finally, apigenin demonstrated potent anti-inflammatory activity in carrageenan induced rat paw edema and delayed type hypersensitivity in the mouse. We conclude that flavonoids offer important therapeutic potential for the treatment of a variety of inflammatory diseases involving an increase in leukocyte adhesion and trafficking.
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PMID:Flavonoids inhibit cytokine-induced endothelial cell adhesion protein gene expression. 763 22

To study the effect of lymphocyte adhesion on the procoagulant activity of endothelial cells, we have stimulated HUVECs with interferon-gamma to upregulate adhesion molecules. Subsequent addition of lymphocytes induced the expression of tissue factor (TF) by HUVECs. Both CD4+ and CD8+ T-cells promoted this TF synthesis via distinct adhesion molecules (CD4+ T-cells: E-selectin and ICAM-1; CD8+ T-cells: MHC-I molecules). In addition, tumor necrosis factor-alpha and -beta (TNF alpha, TNF beta) and platelet-activating factor (PAF) were involved in lymphocyte-mediated TF expression on HUVECs. We demonstrate that PAF plays a pivotal role in this process. Adhesion of lymphocytes to endothelial cell surface molecules induced the release of PAF. PAF, in turn, caused the production of TNF alpha and TNF beta, both of which are potent stimulators of TF expression.
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PMID:Lymphocyte adhesion to human endothelial cells induces tissue factor expression via a juxtacrine pathway. 754 20

Adhesion molecules involved in attachment between human pancreatic carcinoma and activated endothelial cells in vitro were investigated. Basal adhesion occurred between 6 pancreatic carcinoma cell lines and unstimulated human umbilical vein endothelial cells (HUVEC), and augmented basal adhesion to activated HUVEC was only seen when pancreatic cancer cells expressed sialyl Lewisa (SLea) and sialyl Lewisx (SLex). Activation of HUVEC with interleukin 1-beta (IL-1 beta) or tumor necrosis factor-alpha (TNF-alpha), but not with interferon-gamma (IFN-gamma), generated the augmentative basal adhesion. Dose dependence and additive effect were observed in augmentation of the basal adhesion induced by IL-1 beta and/or TNF-alpha. Increase in adhesion correlated with up-regulation of the surface E-selectin (or ELAM-1) on HUVEC, and was evident at both 25 degrees C and 4 degrees C. Anti-E-selectin and anti-SLea blocked the augmented attachment, whereas anti-SLex, an antibody against another known ligand for E-selectin, did not. The collective evidence indicates that attachment between pancreas carcinoma cells and activated endothelial cells is regulated by cytokines such as IL-1 beta and TNF-alpha, and is mediated by SLea on pancreas carcinoma and E-selectin on endothelial cells. These molecules may be of significant importance in blood-borne metastasis of pancreatic carcinoma cells to inflamed sites.
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PMID:Importance of E-selectin (ELAM-1) and sialyl Lewis(a) in the adhesion of pancreatic carcinoma cells to activated endothelium. 768 90

We have previously shown that lymphocytic cells bind to cultured syncytiotrophoblast and that this may be important in the lymphocyte-mediated infection of trophoblast with the human immunodeficiency virus (HIV). Leukocyte-trophoblast adhesion may also have implications for normal trophoblast function. The following experiments were designed to characterize the adhesion systems that mediate the attachment of lymphocytic cells to trophoblast. Adhesion was assayed by labelling lymphocytic MOLT-4, clone 8 cells with the fluorescent marker, calcein-AM, and then incubating them with primary cultures of human syncytiotrophoblast. Adhesion was stimulated by pretreatment of the trophoblast cultures with several cytokines either alone or together. These included tumor necrosis factor-alpha (TNF-alpha), granulocyte/macrophage-colony stimulating factor (GM-CSF), interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN-gamma). Stimulation was time- and dose-dependent. In contrast, preincubation of trophoblast cultures with anti-TNF-alpha antibodies for 2 days reduced MOLT adhesion by almost 50%. Preincubation with other anti-cytokine antibodies had no significant effect on adhesion. In other experiments, adhesion was measured in the presence of antibodies to known adhesion molecules. Adhesion was reduced by 50% in the presence of antibodies to alpha 4 integrin or beta 1 integrin. When present together, these antibodies reduced adhesion by almost 85%. Incubation in the presence of antibodies to the very late activation antigen-4 (VLA-4; alpha 4 beta 1 integrin) counter-receptors, VCAM-1 and CS-1, was without effect. Adhesion was also unaffected by antibodies to LFA-1, ICAM-1, ICAM-2, LFA-2, or LFA-3. These results suggest that adhesion is mediated by an adhesion system consisting of lymphocyte VLA-4 (alpha 4 beta 1) and an as yet unidentified counter receptor on trophoblast.
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PMID:Effect of cytokines and anti-adhesion molecule antibodies on the adhesion of lymphocytic cells to human syncytiotrophoblast. 780 71

Twelve different human primary and metastatic Ewing's sarcoma (ES) and primitive peripheral neuroectodermal tumour (pPNET) cell lines were examined by fluorocytometric analysis for the expression of alpha 1, alpha 2, alpha 3 and alpha 6 very late antigen (VLA) beta 1-integrins. VLA-alpha 1, was abundantly expressed on all typical ES cell lines and pPNET cell lines, while absent from atypical (large cell) ES cells. VLA-alpha 2 was displayed on some ES and pPNET cell lines. In two different pPNET cell lines, derived from the same patient, VLA-alpha 2 expression was considerably higher on primary cells compared with metastatic cells. VLA-alpha 3 was exclusively expressed on pPNET cell lines. Expression of VLA-alpha 6 was higher on metastatic than on primary ES and pPNET cells. Adhesion assays on purified extracellular matrix (ECM) proteins, using monospecific adhesion-blocking antibodies, disclosed VLA-1 (alpha 1 beta 1) on typical ES cells and pPNET cells, and VLA-2 (alpha 2 beta 1) on atypical ES cells, as dual collagen type IV (COIV)/laminin (LM) binding sites, and VLA-6 (alpha 6 beta 1) as a specific LM binding site. Treatment of typical ES cells and pPNET cells for up to 48 h with recombinant human interferon-gamma (rhIFN gamma) and tumour necrosis factor-alpha (rhTNF alpha) upregulated alpha 1 and beta 1 expression, concomitant with an increase in cell adhesion to COIV and LM. Alternatively, these cytokines downregulated the expression of alpha 2, alpha 6 and beta 1 on atypical ES cells, concomitant with a decrease in the adhesion to COIV and LM. In conclusion, these findings suggest that the difference in repertory of CO and LM integrin receptors on ES cells and pPNET cells reflects tumour status and degree of differentiation. Furthermore, our data indicate that IFN gamma- and TNF alpha-mediated alteration in the level of expression of distinct VLAs on ES and pPNET cells is correlated with changes in the adhesive behaviour of these tumour cells.
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PMID:Expression of functional very late antigen-alpha 1, -alpha 2, -alpha 3 and -alpha 6 integrins on Ewing's sarcoma and primitive peripheral neuroectodermal tumour cells and modulation by interferon-gamma and tumour necrosis factor-alpha. 785 12

Early experience with recombinant adenoviruses for gene transfer to airway epithelium suggests that these vectors are associated with the development of inflammation. The mechanisms for this are unclear, but previous work has shown that respiratory viruses can cause increased expression of intercellular adhesion molecule-1 (ICAM-1) on airway epithelial cells. We therefore hypothesized that recombinant adenoviruses may induce ICAM-1 expression and thereby facilitate the development of airway inflammation. To address this, primary cultures of human bronchial epithelial cells were examined for ICAM-1 expression by flow cytometry after infection with a serotype 5, E1/E3-deleted recombinant adenovirus containing the Escherichia coli LacZ reporter gene driven by the cytomegalovirus promoter (Ad.CMVlacZ). Compared with control cells, ICAM-1 expression was unchanged after infection with Ad.CMVlacZ, but increased after infection with wild-type adenovirus. Treatment of Ad.CMVlacZ-infected cells with interferon-gamma (IFN) resulted in increased ICAM-1 expression, but to a lower level than that seen in cells treated with IFN alone, indicating that recombinant adenovirus infection blunted IFN-induced up-regulation of ICAM-1. Adhesion of human leukocytes to human bronchial epithelial cells was not increased after Ad.CMVlacZ infection, thereby excluding an ICAM-1-independent increase in leukocyte-epithelial adhesion. The results for ICAM-1 expression were confirmed in vivo, as immunostaining of human bronchial xenografts infected with Ad.CMVlacZ revealed basilar epithelial staining with ICAM-1, but no increased expression on cells expressing beta-galactosidase. This study demonstrates that unlike other respiratory viruses, recombinant E1/E3-deleted adenovirus does not cause increased ICAM-1 expression on human bronchial epithelium in vitro or in vivo nor increased leukocyte adhesion in vitro.
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PMID:ICAM-1 expression on bronchial epithelium after recombinant adenovirus infection. 786 13

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

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

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

The presence of a putative autoantigen of autoimmune disorder in a target organ may cause accumulation of specific T cells in the inflammatory region. One of the mechanisms of such accumulation involves the migration of specific-circulating T cells through the endothelial cells into the target lesion. The presence of only a few specific T cells responsive to a putative autoantigen has hampered the investigation of specific migration of circulating T cells to the target organ. We used a superantigen to investigate specific T-cell adhesion to endothelial cells, because it stimulates a large proportion of T cells with particular V beta elements and adhesion of T cells to the endothelium is a vital step in the migration process. Adhesion of murine T cells to the human endothelial cell line, EA.hy926, was specifically increased in the presence of staphylococcal enterotoxin B (SEB). The increase was interferon-gamma (IFN-gamma)-dependent, and consisted mainly of CD4+ T cells. V beta 8.1,2+ T cells preferentially adhered to endothelial cells in the presence of SEB compared with V beta 6+ T cells. Pretreatment of endothelial cells with SEB increased the adherence of V beta 8.1,2+ T cells, while anti-human leucocyte antigen (HLA)-DR and -DQ antibodies inhibited the increased adherence of V beta 8.1,2+ T cells. Our results demonstrate that increased T-cell adhesion to endothelial cells is SEB specific, and that the specificity is dependent on major histocompatibility complex (MHC) class II molecules expressed on endothelial cells and on the recognition of the SEB-MHC class II complex by V beta 8.1,2+ T cells.
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PMID:Staphylococcal enterotoxin B-specific adhesion of murine splenic T cells to a human endothelial cell line. 877 62

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