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)

Adhesion of tumor cells to vascular endothelial surfaces is one of the key steps in metastatic dissemination. Several factors are believed to be implicated in the regulation of the adhesive properties of tumor cells. We show that the adhesion of five different tumor cell lines, all of them of human origin, to human umbilical vascular endothelial cells (ECs) significantly increases following pretreatment of ECs with the cytokines interleukin-1 and tumor necrosis factor, whereas tumor cell/EC interactions remained unchanged after incubation with interferon-gamma. Significant augmentation in tumor cell adhesion was also observed when ECs were treated with the lipoxygenase inhibitors salicylate and the compound BW755C. In all cases, increased tumor cell adhesion was concomitant with significant decreases in the EC levels of linoleic acid, lipoxygenase-derived metabolite 13-hydroxy-octadecadienoic acid (13-HODE). On the contrary, pretreatment of the EC monolayers with aspirin did not result in any changes towards tumor cell adhesion. These results suggest that tumor cell/EC interaction is modulated, at least in part, by intracellular levels of 13-HODE and is independent of prostacyclin (PGI2) production by the ECs.
 ...
PMID:Effects of endothelial cell treatment on 13-HODE and prostacyclin synthesis and its correlation with tumor cell-vascular endothelial cell adhesion. 180 Apr 51

Monocytes and endothelial cell interactions play a key role in the development of vascular lesion, inflammation and atherosclerosis. Leukocyte adhesion is mediated through specific molecules CD11/CD18 complexes on the leukocyte side and the ELAM (Leukocyte Adhesion Molecule) ICAM (Intercellular Adhesion Molecule) on the endothelium cell surface. Several monocyte products damage endothelial cells such as free radicals, oxygen peroxides, proteases, hydrolases, lipases... Various monokines alter endothelial cell function and proliferation. Interleukin 1, gamma interferon, alpha tumor necrosis factor increase ELAM, further more they induce the synthesis of procoagulant activity by endothelial cells. Monocyte derived growth factor stimulates endothelial cells proliferation while transforming growth factors, beta (TGF beta) and TNF alpha inhibit endothelial cell growth. Lipid products of monocyte origins such as leukotrienes induce an activation of endothelial cells which results in a production of prostacyclin. Monocytes may also participate in the coagulation process by producing thromboplastin and coagulation factors and facilitating the tenase (activation of factor X) complex formation. On the other hand, monocyte also synthesize tissue plasminogen activator and inhibitor. The numerous factor produced by monocytes may affect in different ways the endothelial cell behavior.
 ...
PMID:[Monocyte-endothelium relations]. 265 10

Two culture surfaces, fibronectin-coated tissue culture grade polystyrene and a surface-modified polystyrene called Primaria (Falcon), were compared. The morphological (contact inhibition and cobblestone aspect), biological (production of von Willebrand factor and prostacyclin) and physiological (growth activity, non-thombogenicity and regeneration after mechanical injury) properties of human endothelial cells were studied. Adhesion and growth of endothelial cells at low and clonal density were identical on both substrates and the biological properties were preserved. Regeneration of injured endothelium was less easy to study on Primaria polystyrene because the extracellular matrix was damaged during the lesion process. Nevertheless, Primaria polystyrene can easily be substituted for fibronectin coating in growth experiments, especially at very low seeding density.
 ...
PMID:Culture of human vascular endothelial cells on a positively charged polystyrene surface, primaria: comparison with fibronectin-coated tissue culture grade polystyrene. 270 6

The inhibition of platelet adhesion by nitric oxide (NO) and prostacyclin and their mechanism of action was studied. Platelet adhesion to collagen fibrils and endothelial cell matrix was inhibited completely by NO but only partially by prostacyclin. Adhesion of platelets to endothelial cell monolayers was inhibited by bradykinin. This effect of bradykinin was unaffected by aspirin, and was accounted for by the amounts of NO released by the endothelial cells. Inhibition of platelet adhesion by NO and prostacyclin was potentiated by selective inhibitors of cGMP phosphodiesterase, but not of cAMP phosphodiesterase, indicating that elevation of cGMP regulates platelet adhesion.
 ...
PMID:The role of nitric oxide and cGMP in platelet adhesion to vascular endothelium. 282 88

Prostacyclin (1 ng to 2 micrograms per ml), which effectively inhibits platelet secretion and aggregation, does not affect adhesion of a proportion of platelets (10-38%) to collagen (50-100 micrograms/ml). Adhesion is not detectable by changes of light transmission (as measured in the optical aggregometer) and is not affected by inhibitors of cyclooxygenase and lipoxygenase enzymes such as indomethacin and compound BW 755C. This adhesion is independent of the collagen concentration (50-400 micrograms/ml) and the incubation time (5-20 min). This suggests that adhesion to collagen is related to a specific platelet population. Adhesion in the presence of prostacyclin, indomethacin and BW 755C occurs in parallel with the formation of a limited amount of phosphatidic acid. Under those conditions it is also possible to observe some phosphorylation of a 40,000 dalton protein which is a substrate for protein kinase C activity. Phosphorylation of the 20,000 dalton protein, or myosin light chain, is less evident. Chlorpromazine (25-100 micrograms/ml) inhibited the adhesion of platelets to collagen, but propanolol (0.5-4 microM) was inactive. The adhesion of platelets to collagen in these experiments parallels the formation of a fraction of phosphatidic acid and 40,000 dalton protein phosphorylation, which are independent of the increased levels of platelet cyclic-AMP induced by high concentrations of prostacyclin. It is also independent of the formation of cyclooxygenase or lipoxygenase products.
 ...
PMID:Adhesion of human platelets to collagen in the presence of prostacyclin, indomethacin and compound BW 755C. 308 71

Adhesion of polymorphonuclear leukocytes (PMN) to the endothelial lining of blood vessels is an essential component of the inflammatory response. We have examined the effects of various lipoxygenase metabolites of arachidonic acid on PMN adhesion to cultured vascular endothelial cells, using a quantitative monolayer adhesion assay. Our results indicated that leukotriene B4 (LTB4) could effectively stimulate PMN adhesion to endothelial cell surfaces, in contrast to the sulfidopeptide leukotrienes C4, D4, and E4, and the monohydroxyacid lipoxygenase products of leukocytes and platelets, 5S-hydroxy-6-trans-8,11,14-cis-eicosatetraenoic acid and 12S-hydroxy-5,8-cis,10-trans,14-cis-eicosatetraenoic acid, respectively. LTB4-stimulation of PMN-endothelial adhesion did not appear to be dependent upon the generation of cyclooxygenase metabolites, nor was it inhibited by exogenous prostacyclin. Enhanced PMN adhesion was observed with endothelial cells that were cultured from different types of large vessels (arteries and veins) in several species. These findings suggest an important pathophysiologic role for LTB4 in regulating leukocyte-vessel wall interactions.
 ...
PMID:Leukotriene B4 stimulates polymorphonuclear leukocyte adhesion to cultured vascular endothelial cells. 609 May 7

We have investigated the regulatory role of PGI2 and its stable analogs, i.e., iloprost and cicaprost, on 12(S)-HETE- and TPA-enhanced tumor cell integrin expression and adhesion. Walker 256 carcinosarcoma cells express alpha IIb beta 3 integrin receptors, which mediate their adhesion to endothelium, subendothelial matrix and fibronectin. Adhesion is enhanced by treatment with exogenous 12(S)-HETE but not 12(R)-HETE or other lipoxygenase-derived hydroxy fatty acids, as well as by TPA. Both 12(S)-HETE and TPA enhanced alpha IIb beta 3 expression on W256 cells. PGI2 iloprost and cicaprost inhibited both 12(S)-HETE- and TPA-enhanced adhesion to endothelium and subendothelial matrix as well as alpha IIb beta 3 expression on W256 cells. The mechanism responsible for the effect of PGI2 was explored. Prostacyclin treatment of W256 cells resulted in an enhanced production of cAMP in a time- and dose-dependent manner. Pre-treatment of tumor cells with increasing concentrations of adenosine resulted in a dose-dependent decrease in the PGI2 effect on TPA or 12(S)-HETE-enhanced adhesion, suggesting that the PGI2 effect is mediated through PKA. Dibutyryl cAMP also blocked the 12(S)-HETE- or TPA-enhanced adhesion, and adenosine pre-treatment did not result in an inhibition of the dibutyryl cAMP effect. Collectively, our results suggest that the cyclooxygenase metabolite PGI2 can antagonize the lipoxygenase metabolite 12(S)-HETE- and TPA-enhanced alpha IIb beta 3 expression and tumor cell adhesion via activation of adenylate cyclase and elevation of intracellular levels of cAMP.
 ...
PMID:Inhibition of TPA and 12(S)-HETE-stimulated tumor cell adhesion by prostacyclin and its stable analogs: rationale for their antimetastatic effects. 753 Feb 35

Erythrocyte-endothelial cell interactions were rediscovered using endothelial cells in culture and radiolabelled erythrocytes. Increased adherence of erythrocytes from patients with sickle cell anaemia was found to be related to the occurrence of vaso-occlusive episodes. In diabetes mellitus and sickle cell anaemia, the adhesion was shown to be potentiated by plasmatic factors such as fibrinogen and fibronectin and to induce endothelial cell activation and enhanced prostacyclin production. The molecular basis of the abnormal adherence of diabetic erythrocytes was shown to be linked to Advanced Glycosylated End-products (AGE) present on the cell membrane and to RAGE 35 receptors exposed by the endothelium. Intercellular Adhesion Molecule (ICAM) was identified as an ubiquitous receptor present on endothelium and involved in leucocyte adhesion and it was more recently demonstrated that erythrocytes infested by Plasmodium falciparum bind to ICAM. This adhesion may be important for the dissemination of Plasmodium falciparum and the complications of the disease. In summary, interactions between endothelium and erythrocytes appear to be involved in the pathophysiology of a number of affections and could constitute a new therapeutic target.
 ...
PMID:Adhesion of erythrocytes to endothelium in pathological situations: a review article. 797 Dec 46

This study investigates the hypothesis that the elevation of intracellular cAMP may affect cytokine-induced expression of adhesion molecules on human vascular smooth muscle cells. In cultured human smooth muscle cells from coronary arteries and saphenous veins, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) induced the expression of intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1), whereas interferon-gamma (INF-gamma) selectively stimulated the expression of ICAM-1. Adenylyl cyclase was stimulated either by the stable prostacyclin mimetic cicaprost or by forskolin. Adhesion molecules were detected by a cell surface enzyme immunoassay and the respective mRNA by reverse transcriptase polymerase chain reaction (rt-PCR). Cicaprost as well as forskolin significantly inhibited TNF-alpha- and IL-1 beta-induced cell surface expression of ICAM-1 and VCAM-1. Semiquantitative rt-PCR measurements showed a marked decrease of TNF-alpha- and IL-1 beta-induced mRNA levels of both adhesion molecules after preincubation with cicaprost. The stability of TNF-alpha-induced ICAM-1 and VCAM-1 expression at mRNA and protein level was not altered by cicaprost. The IFN-gamma-induced increase of cell surface expression of ICAM-1 and the respective mRNA levels, however, were not significantly altered by elevation of intracellular cAMP. Basal and stimulated cAMP levels, measured by radioimmunoassay, did not differ in TNF-alpha- and IFN gamma-treated cells. The present results demonstrate that the expression of adhesion molecules on human smooth muscle cells induced by cytokines is differentially modulated by activation of adenylyl cyclase.
 ...
PMID:Regulation of tumor necrosis factor alpha- and interleukin-1-beta-induced induced adhesion molecule expression in human vascular smooth muscle cells by cAMP. 940 29

The vascular endothelium influences not only the three classically interacting components of hemostasis: the vessel, the blood platelets and the clotting and fibrinolytic systems of plasma, but also the natural sequelae: inflammation and tissue repair. Two principal modes of endothelial behaviour may be differentiated, best defined as an anti- and a prothrombotic state. Under physiological conditions endothelium mediates vascular dilatation (formation of NO, PGI2, adenosine, hyperpolarizing factor), prevents platelet adhesion and activation (production of adenosine, NO and PGI2, removal of ADP), blocks thrombin formation (tissue factor pathway inhibitor, activation of protein C via thrombomodulin, activation of antithrombin III) and mitigates fibrin deposition (t- and scuplasminogen activator production). Adhesion and transmigration of inflammatory leukocytes are attenuated, e.g. by NO and IL-10, and oxygen radicals are efficiently scavenged (urate, NO, glutathione, SOD). When the endothelium is physically disrupted or functionally perturbed by postischemic reperfusion, acute and chronic inflammation, atherosclerosis, diabetes and chronic arterial hypertension, then completely opposing actions pertain. This prothrombotic, proinflammatory state is characterised by vaso-constriction, platelet and leukocyte activation and adhesion (externalization, expression and upregulation of von Willebrand factor, platelet activating factor, P-selectin, ICAM-1, IL-8, MCP-1, TNF alpha, etc.), promotion of thrombin formation, coagulation and fibrin deposition at the vascular wall (expression of tissue factor, PAI-1, phosphatidyl serine, etc.) and, in platelet-leukocyte coaggregates, additional inflammatory interactions via attachment of platelet CD40-ligand to endothelial, monocyte and B-cell CD40. Since thrombin formation and inflammatory stimulation set the stage for later tissue repair, complete abolition of such endothelial responses cannot be the goal of clinical interventions aimed at limiting procoagulatory, prothrombotic actions of a dysfunctional vascular endothelium.
 ...
PMID:Endothelial function and hemostasis. 1079 71


1 2 Next >>