| Background:The urokinase-mediated plasminogen activaton system is involved in many physiologic and pathological events that include cell migration and tissue remodeling. This system also plays an important role in the process such as inflammation, angiogenesis, atherogenesis and tumor invation and metastasis. The urokinase-type plasminogen activator receptor(uPAR) is a key molecular of this system and can bind extracellular and cell membrane molecular such as urokinase type plasminogen activator(uPA), vitronectin(VN), integrins and so on. Independently of cell suface-associated proteolysis, uPAR is involved in several cellular functions like adhesion, proliferation and chemotaxis, all of which are fundamental processes in atherogensis. More and more studies show that local and systemic inflammation plays an important role in the development of atherogensis. Leukocytes adhesion to vascular endothelial cells is the earliest pathologicalchange in atherosclerosis and Leukocyte migration through endothelial cells to the vessel wall space is the necessary stept to issue damage and inflammation. During this process, the leukocytes adhesion to vascular endothelial is the most important part. CD11b/CD18, which belongs to the family of integrins, is a kind of uPAR's ligand. It can form complexs with uPAR to mediate cell adhesion. Leukocytes adhesion on endothelial cells is based on the interaction between CD lib/CD 18 and its ligand - intercellular adhesion molecule-1 (ICAM-1, CD54) which is expressed on endothelial cells. Phosphatidylinositolspecific phosphlipase C (PI-PLC) and nicotinamide adenine dinucleotide glycohydrolase (NADG) can break the complexs from the cell surface.Objective:Our study was aiming to evaluate the atherogenic role of uPAR, CD11b/CD18 expressed on human monocytes and neutrophilic granulocytes, and the influence on the capacity of monocyte adhesion. We tried to investigate the effects of oxLDL and high glucose on uPAR, CD11b/CD18 expression on monocyte, and also tried to investigate the different influences on monocyte binding capacity for human umbilical vein endothelial cells between uPAR antibody, CD11b antibody, NADG, PI-PLC and ICAM-1 antibodyMethods:The study group comprised 26 patients presenting with AMI within 24 hours after the onset of pain. 23 patients with OMI, and 20 healthy volunteers were studied as control group. Mean fluorescence intensity and the proportion of peripheral monocytes and neutrophilic granulocytes expressing uPAR, CD11b/CD18 were measured by flow cytometer. Monocytes were separated and purified by density gradient centrifugation and adhering assay. In vitro, we incubated the cells with oxLDL and high glucose, and we measured uPAR, CD11b/CD18 by ELISA. Anti-uPAR, anti-CD11b, NADG, PI-PLC, anti-ICAM-1 were incubated with monocytes together to investigate their different influences on monocyte binding capacity for human umbilical vein endothelial cells.Results:Surface expression of uPAR and CD11b/CD18 were both significantly higher on peripheral monocytes and neutrophilic granulocytes in patients with AMI, compared with that in patients with OMI and healthy volunteers (p<0.05). Neither surface expression of uPAR nor CD11b/CD18 had significant differences between the patients with OMI and healthy volunteers. In vitro, oxLDL and high glucose could significantly increased the expression of uPAR and CD11b/CD18 on monocytes, and also enhanced the capacity of monocyte adhesiveness compared with that of control group (p<0.05). The capacity of monocytes binding for human umbilical vein endothelial cells was significantly stronger in patients with AMI compared with that in patients with OMI and healthy volunteers (p<0.05). There are no significant differences between the patients with OMI and healthy volunteers on the capacity of monocytes binding for human umbilical vein endothelial cells. Adhesion of monocytes was effectively inhibited by anti-uPAR and anti-CD11b. Adhesion of monocytes was almost inhibited to a same level especially by NADG, PI-PLC, anti-ICAM-1.Conclusions: Our study showed both uPAR and CD11b/CD18 surface expression on monocytes and neutrophilic granulocytes in patients with AMI were significantly increased compared with that in the patients with OMI and healthy volunteers. At the same time, the capacity of monocytes adhesion was also significantly stronger in patients with AMI. There are no significant differences between the patients with OMI and healthy volunteers either in uPAR, CD11b/CD18 expression or in capacity of monocytes adhesion. OxLDL and high glucose not only increased the expression of uPAR and CD11b/CD 18 on monocytes significantly, but also enhanced the capacity of monocyte adhesion. Our study showed hyperlipidemia and pathoglycemia, which are two important high risk to coronary artery disease, were probably a critical pair of factors in activating uPAR,CD11b/CD18 expression and enhancing capacity of adhesion on monocytes. Adhesion of monocyte could be effectively inhibited by using several antibodys. Our results provided new knowledge of monocytes atherogenic role by uPAR and CD11b/CD18, and further investigation was required to elucidate its mechanism and the possibility of clinical application. These might provide a new way for preventing and treating coronary artery disease.
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