UMLS:C0001511 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

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

Dietary copper deficiency impairs the function of both the vascular endothelium and circulating leukocytes. In the current study, leukocyte-endothelium adhesion was observed in the in vivo cremaster muscle microcirculation of copper-adequate and copper-deficient rats. Male, weanling Sprague-Dawley rats were fed purified diets that were either adequate (5.6 microg/g) or deficient (0.3 microg/g) in copper. Adhesion was stimulated with the inflammatory mediators tumor necrosis factor-alpha and bradykinin, and the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine. Intravascular adhesion of leukocytes to the vascular endothelium was significantly attenuated in the copper-deficient group in response to all three agonists. These results occurred without any difference in intravascular wall shear rate between the dietary groups. Based on previous work, we propose that the attenuated response is caused by either decreased expression of adhesion molecules on leukocytes and endothelial cells or by inhibition of the endothelial cell calcium signaling associated with copper deficiency.
...
PMID:Leukocyte-endothelial adhesion is impaired in the cremaster muscle microcirculation of the copper-deficient rat. 1127 33

Carcinoembryonic antigen (CEA) has been reported to promote the metastatic potential in some experimental tumors. Adhesion molecules are known to play an important role in the process of metastasis. Cytokines, including interleukin 1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), which are produced by Kupffer cells, induce endothelial cells to express adhesion molecules. As a result, the present study was designed to investigate whether the interaction between CEA and Kupffer cells accelerated the metastatic potential of tumors in the liver. Kupffer cells isolated from the liver of male BALB/c mice were cultured with CEA, either with or without the addition of a cytokine inhibitor. The levels of IL-1beta and TNF-alpha were examined in a culture medium. An adhesion assay of colon cancer cell lines to human umbilical vein endothelial cells was also performed. When CEA was added to the Kupffer cell culture medium, cytokines were produced. Elevated levels of cytokines appeared to lead to increased rates of adhesion of cancer cells to endothelial cells. However, these phenomena were blocked by the addition of cytokine inhibitors. CEA stimulated Kupffer cells to produce cytokines. An elevated number of cytokines have been proven to promote the expression of adhesion molecules in endothelial cells. These processes are therefore considered to contribute to the metastasis of malignant cells to the liver. These results suggest that cytokine inhibitors may therefore play an important role in the inhibition of hepatic metastasis.
...
PMID:Role of carcinoembryonic antigen in the progression of colon cancer cells that express carbohydrate antigen. 1128 55

Adhesion molecules on endothelial cells play an important role in leukocyte recruitment in several inflammatory processes. Vascular selectins mediate the initial adhesion of leukocytes to the blood vessel wall during their extravasation into inflamed tissues, and in vitro studies in dogs have shown that selectin expression can be induced by cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1). The objective of this study was to determine whether vascular selectins are induced by cytokines in vivo in a cutaneous model of inflammation in dogs. Skin biopsies were collected from nine dogs at various time points after an intradermal injection of TNF-alpha (10 ng/site) or phosphate-buffered saline containing 0.1% bovine serum albumin, and immunohistochemistry was performed using anti-P-selectin (MD3) and anti-E-selectin (CL37) monoclonal antibodies. In all animals, TNF-alpha induced an inflammatory reaction that was maximal at 12 hours and then decreased by 24 and 48 hours. Control skin displayed no expression of E- and P-selectin, whereas TNF-alpha induced the expression of P-selectin and E-selectin on dermal vessels that was highest at 12 hours and 3 hours, respectively (P < 0.05). Numerous platelet aggregates recognized by the anti-P-selectin antibody were present in the lumina of vessels and in perivascular tissues. These results demonstrate that TNF-alpha can induce the expression of P- and E-selectin in vivo in dog skin and suggest that these selectins are involved in leukocyte recruitment in canine dermatitis.
...
PMID:Expression of E- and P-selectin in tumor necrosis factor-induced dermatitis in dogs. 1135 55

Enoxaparin is a low molecular weight heparin, widely accepted as anticoagulant or antithrombotic drug, and is likely to have a role in acute inflammation. To evaluate the anti-inflammatory potential of enoxaparin, we investigated the direct effect of the drug on the activation of endothelial cells. For this purpose we set up an in vitro system in which cultured valvular endothelial cells (VEC) activated by tumor necrosis factor alpha or lipopolysaccharide were exposed to a monocytic cell line; these conditions induced a significant adhesion of monocytes to VEC. Adhesion assays, ELISA, and flow cytometric analysis revealed that pretreatment with enoxaparin, at a relevant plasma concentration (16 microg/ml), acts upon activation of VEC by inhibition of lipopolysaccharide-induced E-selectin expression and tumor necrosis factor stimulated ICAM-1 expression, thus reducing monocyte adhesion to VEC. These results suggest a novel function of enoxaparin, namely to protect VEC from activation and inhibiting the expression of cell adhesion molecules.
...
PMID:A novel attribute of enoxaparin: inhibition of monocyte adhesion to endothelial cells by a mechanism involving cell adhesion molecules. 1190 Dec 99

Mast cells (MCs) are central to asthma and other allergic diseases, and for responses to infection and tissue injuries. MCs arise from committed progenitors (PrMCs) that migrate from the circulation to tissues by incompletely characterized mechanisms, and differentiate in situ in perivascular connective tissues of multiple organs. PrMCs derived in vitro from human cord blood were examined for adhesion molecule expression and their ability to adhere to human umbilical vein endothelial cells (HUVECs) under conditions that mimic physiologic shear flow. The PrMCs expressed alpha(4)beta(1), low levels of beta7, and the beta2-integrins alphaLbeta2 and alphaMbeta2. The PrMCs also expressed PSGL-1, but not L-selectin. At low (0.5 dynes/cm(2)-1.0 dynes/cm(2)) shear stress, PrMCs attached and rolled on recombinant E-selectin and P-selectin and VCAM-1. An anti-PSGL-1 monoclonal antibody (mAb) blocked essentially all adhesion to P-selectin but reduced adhesion to E-selectin by only 40%, suggesting PrMCs express other ligands for E-selectin. PrMCs adhered strongly to tumor necrosis factor-alpha (TNF-alpha)-activated HUVECs, whereas adhesion to interleukin 4 (IL-4)-activated HUVECs was lower. PrMC adhesion to IL-4-activated HUVECs was totally alpha4-integrin- and VCAM-1-dependent. Adhesion to TNF-alpha-activated HUVECs was blocked by 50% by mAbs against alpha4-integrin, vascular cell adhesion molecule-1 (VCAM-1), E-selectin, or PSGL-1, whereas combinations of mAbs to alpha4-integrin plus PSGL-1, or VCAM-1 plus E-selectin, blocked adhesion by greater than 70%. Thus, PrMCs derived in vitro predominantly use alpha4-integrin, VCAM-1, PSGL-1, and other ligands that bind E-selectin for adhesion to cytokine-activated HUVEC monolayers. These observations may explain the abundance of MCs at sites of mucosal inflammation, where VCAM-1 and E-selectin are important inducible receptors.
...
PMID:Human mast cell progenitors use alpha4-integrin, VCAM-1, and PSGL-1 E-selectin for adhesive interactions with human vascular endothelium under flow conditions. 1192 79

Adhesion molecules are known to be an important part of leukocyte migration and extravasation in both homeostatic and inflammatory conditions. Intracellular adhesion molecule-1 (ICAM-1 or CD54) is constitutively expressed on endothelial cells and is up-regulated during acute and chronic inflammation. We investigated the efficacy and consequences of interfering with CD54 after administration of an antisense oligonucleotide to ICAM-1 (CD54) in the transgenic HLA-B27/beta2 microglobulin rat model. One hundred percent of the HLA-B27 transgene + animals will spontaneously develop chronic inflammation (some more severely than others) in the gastric mucosa, cecum, and colon. We carried out two studies, i.p. injection and rectal administration of antisense. Following i.p. and rectal treatment, there were significant decreases in colonic mucosal wall thickness, histologic inflammation, CD54 expression in the colon and peripheral blood, and the percentage of colon weight per end body weight. Furthermore, decreased expression of CD49d, CD18, and tumor necrosis factor-alpha was observed in antisense treated rats. Therefore, the HLA-B27 transgenic model of spontaneous and chronic inflammatory bowel disease, which has increased expression of adhesion molecules, responds to both routes of administration of ICAM-1 antisense oligonucleotides. These studies support the regulatory role of adhesion molecules in chronic intestinal inflammation, the need for an understanding of how the route of drug delivery can alter the dose and area affected, and finally the role of antisense oligonucleotides as a therapeutic modality in chronic spontaneous inflammatory bowel diseases.
...
PMID:Amelioration of chronic and spontaneous intestinal inflammation with an antisense oligonucleotide (ISIS 9125) to intracellular adhesion molecule-1 in the HLA-B27/beta2 microglobulin transgenic rat model. 1218 46

We studied the effect of atorvastatin on the adhesive phenotype of human endothelial cells (HUVEC) stimulated by tumor necrosis factor (TNF)-alpha. Surface expression of adhesion molecules on HUVEC was examined by flow cytometry and confocal microscopy, and adhesion of monocytes (human THP-1 cell line) was measured in vitro under flow conditions. In TNF-alpha-activated HUVEC, atorvastatin significantly enhanced surface expression of vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-1, E-selectin, and fractalkine, when compared with TNF-alpha stimulation alone. This enhancement was reversed by mevalonate or geranylgeranyl pyrophosphate (GGPP) and was mimicked by an inhibitor of geranylgeranylation. The enhancing effect of atorvastatin was restricted to TNF-alpha-inducible adhesion molecule and was the reflect of an increased protein synthesis (mRNA and protein) and not of a reduced shedding. Confocal microscopy examination showed that atorvastatin also altered the surface distribution of adhesion molecules. Adhesion of human THP-1 cells on TNF-alpha-activated HUVEC was significantly reduced by atorvastatin (-42% at 1 microM). Mevalonate or GGPP restored the TNF-alpha-induced adhesive potential. These results show that atorvastatin, by inhibiting prenylation of G proteins, enhances the TNF-alpha-induced expression of adhesion molecules at the endothelial cell surface and also alters their surface distribution which may account for the reduced binding of monocytes.
...
PMID:Effect of atorvastatin on adhesive phenotype of human endothelial cells activated by tumor necrosis factor alpha. 1254 94

The aim of this study was to quantify the expression of E-selectin, intercellular cell adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vascular endothelial cells (HUVECs) exposed to anoxia/reoxygenation (A/R) in the presence or absence of an inflammatory context (0.1 IU/ml tumor necrosis factor-alpha [TNF-alpha]) and to investigate the effects of two different NADPH inhibitors, apocynin and diphenyleneiodonium (DPI), on the expression of the endothelial cell adhesion molecules. Confluent HUVECs were exposed to anoxia for 3 hours (100% N2), followed by a reoxygenation period of 4 hours. TNF-alpha at 0.1 IU/ml was added to the medium either under normoxic conditions for 7 hours (TNF-alpha) or just before the start of anoxia (A/R + TNF-alpha). Levels of E-selectin, VCAM-1, and ICAM-1 were quantified using specific monoclonal antibodies revealed by an alkaline phosphatase-labeled goat F(ab)'2 fragment against mouse IgG antibody and the fluorescent substrate Attophos. Adhesion experiments were also performed using calcein-labeled U937 leukocytes. HUVECs submitted to A/R overexpressed E-selectin but not VCAM-1 or ICAM-1, whereas TNF-alpha at 0.1 IU/ ml increased the expression of all three adhesion molecules. In endothelial cells subjected to A/R in the presence of TNF-alpha, a synergistic increase of E-selectin expression and a synergistic adhesion of U937 cells was noted. The NADPH oxidase inhibitors apocynin and DPI both decreased significantly the U937 adhesion and the E-selectin overexpression on HUVECs submitted to A/R, TNF-alpha, or A/R + TNF-alpha. These results suggest that E-selectin expression is implicated in the leukocyte adhesion to HUVECs caused by A/R in the presence or absence of an inflammatory context. NADPH oxidase appears to participate in the E-selectin overexpression on HUVECs subjected either to A/R and/or TNF-alpha, suggesting a major role of this enzyme in the ischemia/reperfusion syndrome.
...
PMID:Effect of NADPH oxidase inhibition on E-selectin expression induced by concomitant anoxia/reoxygenation and TNF-alpha. 1257 57

1,3,5,6-tetrahydroxyxanthone was synthesized. The relationship between protective effect of xanthone on endothelial cells and endogenous nitric oxide synthase inhibitors was investigated. Endothelial cells were treated with ox-LDL (100 microg/mL) for 48 h. Adhesion of monocytes to endothelial cells and release of lactate dehydrogenase (LDH) was determined. Levels of tumor necrosis factor-alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1), nitric oxide (NO) and asymmetric dimethylarginine (ADMA, an endogenous inhibitor of nitric oxide synthase) in conditioned medium and activity of dimethylarginine dimethylaminohydrolase (DDAH) in endothelial cells were measured. Incubation of endothelial cells with ox-LDL (100 microg/mL) for 48 h markedly enhanced the adhesion of monocytes to endothelial cells, increased the release of LDH, the levels of TNF-alpha, MCP-1 and ADMA, and decreased the content of NO and the activity of DDAH. Xanthone (1,3,5,6-tetrahydroxyxanthone) (1, 3 or 10 micromol/L) significantly inhibited the increased adhesion of monocytes to endothelial cells and attenuated the increased levels of LDH, MCP-1 and ADMA induced by ox-LDL. Xanthone (1,3,5,6-tetrahydroxyxanthone) (3 or 10 micromol/L) significantly attenuated the increased level of TNF-alpha and decreased level of NO and activity of DDAH by ox-LDL. The present results suggest that xanthone (1,3,5,6-tetrahydroxyxanthone) preserves endothelial cells and inhibits the increased adhesion of monocytes to endothelial cells induced by ox-LDL, and that the protective effect of xanthone (1,3,5,6-tetrahydroxyxanthone) on endothelial cells is related to reduction of ADMA concentration via increase of DDAH activity.
...
PMID:Relationship between protective effect of xanthone on endothelial cells and endogenous nitric oxide synthase inhibitors. 1460 80

Neutrophil adhesion to extracellular matrix is necessary for an effective inflammatory response. Adhesion may accelerate neutrophil activation by affecting intracellular signaling pathways. The nuclear transcription factor kappaB (NF-kappaB) controls several cellular functions, including inflammation, proliferation, and cell survival. We explored the role of adhesion in NF-kappaB activation in human neutrophils. Cells were stimulated with tumor necrosis factor-alpha (TNF-alpha), granulocyte macrophage-colony-stimulating factor (GM-CSF), interleukin-8 (IL-8), and formyl-methionyl-leucyl-phenylalanine (fMLP). All four initiated neutrophil adherence to and spreading on fibronectin. GM-CSF and IL-8 did not activate NF-kappaB in suspended neutrophils but rapidly activated NF-kappaB under adherent conditions on matrix, as shown by IkappaB kinase activity assay, IkappaBalpha degradation, electromobility shift assay, and quantitative reverse transcriptase-PCR. In contrast, TNF-alpha activated NF-kappaB both in suspended cells and adherent cells. fMLP did not activate NF-kappaB in either suspended or adherent cells. Specific beta(2) integrin blockade prevented NF-kappaB activation by GM-CSF and IL-8 on fibronectin. Co-stimulating CD18 and CD11b with activating antibodies resulted in NF-kappaB activation by GM-CSF and IL-8 in suspended cells. We inhibited actin polymerization with cytochalasin and blocked the non-receptor kinase Syk with piceatannol. Both maneuvers prevented the co-stimulatory NF-kappaB-activating signal by beta(2) integrins. Thus, in addition to beta(2) integrin ligand binding, NF-kappaB activation depended on the formation of the receptor-associated intracellular focal adhesion complex. We conclude that beta(2) integrins may provide co-stimulatory signals allowing some soluble mediators to activate the NF-kappaB pathway even when they are not capable of doing so in suspension. This effect may become important when human neutrophils leave the circulating blood and migrate through extracellular matrix during inflammation.
...
PMID:Integrins and cytokines activate nuclear transcription factor-kappaB in human neutrophils. 1461 35

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>