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

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.
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PMID:[Monocyte-endothelium relations]. 265 10

Various collagen-based materials were used to assess the structural requirements of collagen for inducing the procoagulant response of adhering platelets, as well as the collagen receptors involved. Cross-linked or monomeric collagen-related peptide (CRP), Gly-Cys-Hyp-(Gly-Pro-Hyp)10-Gly-Cys-Hyp-Gly was highly adhesive for platelets in a glycoprotein VI-(GpVI-)dependent manner. Adhesion was followed by a prolonged increase in cytosolic [Ca2+]i, formation of membrane blebs, exposure of phosphatidylserine (PS) and generation of prothrombinase-stimulating activity. Fibrils of type-I collagen were less adhesive but, once adhered, many of the platelets presented a full procoagulant response. Monomeric type-I collagen was unable to support adhesion, unless Mg(2+)-dependent integrin alpha2beta1 interactions were facilitated by omission of Ca2+ ions. With all surfaces, however, post-addition of CaCl2 to adhering platelets resulted in a potent Ca(2+)-influx signal, followed by PS exposure and bleb formation. The procoagulant response elicited by binding to CRP was inhibited by anti-GpVI Fab fragments, but not by impeding integrin alpha2beta1-mediated events. With fibrillar collagen, it was inhibited by blocking either the GpVI- or integrin alpha2beta1-mediated interactions. This suggests that the triple-helical Gly-Pro-Hyp repeat in CRP and analogous sequences in fibrillar collagen stimulate the procoagulant response of adherent platelets by acting as ligands for GpVI. Influx of Ca2+ is required for this response, and adhesion via integrin alpha2beta1 serves to potentiate the signaling effects of GpVI.
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PMID:Function of glycoprotein VI and integrin alpha2beta1 in the procoagulant response of single, collagen-adherent platelets. 1036 54

In order to understand some of the haemostatic mechanisms in rats for the interpretation of toxicological data, basic haemostatic parameters with a special emphasis on platelet functions were first measured in vitro. The results of reactions of rat platelets to many aggregating agents suggest that only ADP may be a consistently significant aggregator. The search for physiologic aggregators revealed ADP to be available from erythrocytes. Adhesion reaction also required ADP. Collagen was not considered to be essential for either reaction. Aggregation and adhesion were probably both reversible in flowing blood, while irreversible thrombi were formed in blood at rest ex vivo. Blood coagulation parameters determined revealed that the intrinsic pathway may be more important than the extrinsic one. The rate of intrinsic coagulation reaction was rapid, and plasma coagulation appeared to be of primary importance while the influence of platelet aggregation was minor. A simple model of rat haemostatic mechanism is proposed based on these results. Additionally, to define the relative contribution of platelets versus other cellular and plasma coagulation in vivo, rats were administered antiplatelet drugs (ticlopidine, suprofen and clopidogrel) and an anticoagulant (warfarin) intraperitoneally. Bleeding times (BTs) were significantly increased in all treated groups. ADP-induced platelet aggregations were significantly depressed by the administration of the three antiplatelet drugs, while kaolon-activated partial thromboplastin time and prothrombin time were greatly increased in the warfarin-treated rats. The increase in BT may be due to the inhibition of platelet activity or blood coagulation defect in rats given antiplatelet drugs or warfarin, respectively. These results suggest that platelets play a key role in haemostasis in the rat. Two possible explanations of the disparity between in vitro and in vivo results may be that functional tests used here are not adequate to cover the properties of rat platelets or that mechanisms leading to the formation of platelet thrombi in rats are ADP-dependent adhesion and ADP-induced aggregation.
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PMID:Characteristics of rat platelets and relative contributions of platelets and blood coagulation to haemostasis. 1071 61

Adhesion of platelets to immobilized collagen induces the expression of anionic phospholipids, e.g. phosphatidylserine (PS), in the outer leaflet of the plasma membrane of these platelets. In contrast, of the platelets that adhere to immobilized fibrinogen only a small sub-population representing 10 +/- 3% of the total population of the fibrinogen-adherent platelets has exposed PS as probed by annexin V binding. Although the presence of PS is thought to be critical for thrombin generation at the platelet surface, no information is available about the effect of this differential PS exposure on the ability of adherent platelets to support thrombin generation. Perfusion of the fibrinogen- or collagen-adherent platelets with solutions containing factor Xa and prothrombin resulted in thrombin generation that i) increased linear during the first perfusion minutes, ii) was about two-fold faster at collagen-adherent than at fibrinogen-adherent platelets and iii) was for more than 98% restricted to the surface of the adherent platelets. It appeared that the lower thrombin generating capacity of fibrinogen-adherent platelets is not due to a lower overall surface density of PS, but is caused by lower amounts of platelet-bound factor Va. Firstly, in both cases thrombin generation could be completely attenuated with antibodies against human factor Va, and secondly, in the presence of an excess of exogenous plasma-derived factor Va similar initial rates of thrombin formation were measured for collagen- and fibrinogen-adherent platelets. Our findings suggest a unique role for immobilized collagen in maintaining haemostasis.
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PMID:Contribution of platelet-derived factor Va to thrombin generation on immobilized collagen- and fibrinogen-adherent platelets. 1168 47

Cross-reactivity with integrins other than glycoprotein IIb/IIIa (GP IIb/IIIa) is discussed as a potential reason for the overall clinical benefits of the GP IIb/IIIa-blocking antibody-fragment abciximab. We evaluated whether abciximab binds to the leukocyte integrin Mac-1, whether it inhibits binding of the distinct ligands and thereby may modulate inflammation, cell proliferation and coagulation. Binding of fluorescence-labelled abciximab to phorbolmyristate acetate-stimulated monocytes and to a monocytic cell line (THP-1) could be detected in flow cytometry. The binding of fibrinogen, the inactivated complement factor 3b (iC3b), and the coagulation factor X to Mac-1 could be inhibited by abciximab (10 microg/ml) in vitro. As a functional consequence, the conversion of factor X to factor Xa mediated by Mac-1, as detected by the chromogenic substrate SZ-2222, was impaired by abciximab. Adhesion of THP-1 cells to immobilized intercellular adhesion molecule 1 (ICAM-1) and to fibrinogen was reduced significantly by abciximab. Fibrinogen-mediated cell aggregation was also impaired. In conclusion, we describe binding of abciximab to Mac-1 on stimulated monocytes. Thereby, abciximab inhibits binding of the ligands fibrinogen, ICAM-1, iC3b and factor X. Furthermore, we demonstrated that Mac-1-dependent conversion from factor X to factor Xa is impaired by abciximab, arguing for the direct modulation of the coagulation cascade by abciximab. Overall, the inhibition of Mac-1 could provide additional clinical benefits of abciximab beyond the well-described blockade of GP IIb/IIIa.
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PMID:The GP IIb/IIIa inhibitor abciximab (c7E3) inhibits the binding of various ligands to the leukocyte integrin Mac-1 (CD11b/CD18, alphaMbeta2). 1243 77

Contrast media (CM) are reported to possess both prothrombotic and anticoagulant properties. The mechanisms are not clearly understood, and early reports are contradictory. To study the effects of CM on haemostasis, we analysed the ex vivo effects of ioversol and iodixanol on platelet adhesion and P-selectin expression, and the in vitro effects of ioversol, iodixanol and ioxaglate on platelet adhesion, P-selectin expression and plasma coagulation. A novel enzymatic assay was used to measure platelet adhesion to protein surfaces, and an enzyme-linked immunosorbent assay was used to measure platelet P-selectin surface expression. Prothrombin time (PT) and activated partial thromboplastin time (APTT) were used to measure plasma coagulation. The ex vivo study consisted of blood from 27 outpatients administered ioversol and 9 patients administered iodixanol intravenously. Samples were collected before and 5 min after CM administration. Healthy donors were used for the in vitro studies on the effects of CM. The ex vivo study showed significantly (p<0.05) decreased platelet adhesion and P-selectin expression after administration of ioversol and iodixanol. Adhesion was more affected than P-selectin expression. The in vitro study showed that ioversol, iodixanol and ioxaglate significantly (p<0.05) and dose-dependently (beginning at 3 mg ml(-1)) decreased platelet adhesion and P-selectin expression. APTT and PT were significantly (p<0.01) prolonged at concentrations of 10 mg ml(-1) and 30 mg ml(-1), respectively. In conclusion, ioversol, iodixanol and ioxaglate inhibit platelet adhesion and P-selectin expression, as well as plasma coagulation. Platelets are more sensitive in relation to the inhibiting effect on plasma coagulation.
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PMID:Similar inhibition of platelet adhesion, P-selectin expression and plasma coagulation by ioversol, iodixanol and ioxaglate. 1954 76