Cell Adhesion, Influence Factors And Adhesion Molecule Gene Modulation

Adhesion of leukocyte to platelet, endothelial cell (EC) and vascular smooth muscle cell (SMC), is an essential component of various acute and chronic cardiovascular diseases including atherosclerosis, thrombosis, reperfusion injury and restenosis after percutaneous transluminal coronary angioplasty etc. Inhibition of cells adhesion of pathological status is effective in reducing the tissue injury induced by acute or chronic inflammations and in preventing the genesis and progress of the diseases mentioned above. It is known that several factors influence the cells adhesion. To study these regulating factors, especially drugs, may be of considerable importance for basic theory and clinical application.The adhesion of leukocyte/platelet was very low in healthy volunteers and normal animals. It was increased dramatically in patients with acute myocardial ischaemia (AMI) or experimental pathological animal models. The results indicated that the activation of both leukocyte and platelet played an important role in increasing both cells adhesion in AMI. The leukocyte/platelet adhesion rate was also increased when platelets were stimulated by thrombin in vitro. The adhesion of leukocyte/platelet was Ca²⁺ dependent, heparin or dextran sulfate inhibited both cells binding but not dextran. This indicates that adhesion molecule—GMP-140 might be involved in the mechanism of leukocyte/platelet adhesion. In addition, the expression of CDlla and CD 11b on the surface of leukocyte in AMI patients was significantly increased than normal subjects. It suggests that the adhesion molecules— CD11a/CD18 and CD11b/CD18 may mediate leukocyte/platelet adhesioaQuercetin inhibited the leukocyte/platelet adhesion in AMI animals when administered intravenously before the formation of AMI model or before the platelet stimulated by thrombin. Aspirin had similar effects as quercetin.The results showed that unactivated leukocyte inhibited platelets aggregation. Both quercetin and aspirin enhanced the inhibitory effects of leukocyte on platelet activation. However, the inhibition of platelet aggregation was disappeared when leukocyte was activated by PMA. It is interested to find out that if incubation of quercetin with platelets before activation of leukocyte by PMA, the inhibitory effect of leukocyte on platelet aggregation was restored. It indicates that quercetin has the ability to prevent the activation of leukocyte by PMA.TNF_α increased the adhesion of EC to leukocyte both time- and dose-dependently. More monocytes bound to EC than neutrophils, and it became more significant with the prolongation of stimulation time. Anti-ICAM-1, anti-E-selectin and anti-VCAM-1 monoclonal antibodies blocked the binding of TNF_α stimulated EC to leukocyte, suggesting that the adhesion molecules, ICAM-1, E-selectin and VCAM-1, mediated both cells adhesion.ELISA and flow cytometric analysis revealed that the expression of ICAM-1 and...