Regulation of thrombin generation at cell surfaces.
A complex series of reactions are involved in the assembly, function, and regulation of the prothrombinase complex. Since the enzyme is multicomponent in nature and each component is required for catalytic function, modulation of enzymatic activity can be achieved in a variety of ways. In addition, since complex assembly so profoundly affects reaction rates, mechanisms that perturb complex formation either positively or negatively have a profound effect on thrombin generation and its local physiologic effects. All of the cells that support prothrombinase assembly and hence thrombin generation respond to thrombin in a variety of ways. Thrombin selectively binds to thrombomodulin and heparin-like molecules expressed on the endothelial cell surface. Thrombin induces the release (and possible synthesis of) prostacyclin, plasminogen activator inhibitor, platelet-derived growth factor, and interleukin-1 and inhibits the release of plasminogen activator from vascular endothelium. Interleukin-1 is a potent mediator of inflammatory phenomena as well as an inducer of tissue factor synthesis in vascular endothelium. With respect to platelets, thrombin selectively binds and stimulates the platelet release reaction and subsequent aggregation. The thrombin-induced release of platelet-derived growth factor from both platelets and vascular endothelium may play a role in inflammation, wound healing, and atherogenesis. Thrombin itself is a potent mitogen of mesenchymal cells, and more recently has been shown to be not only a chemoattractant, but also a mitogen for monocytes. Thrombin also appears to bind selectively to monocytes and in so doing induces release of interleukin-1. Thrombin affects a myriad of cellular responses related to hemostasis, thrombosis, inflammation, would repair, and atherogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001777:Blood Coagulation; D001792:Blood Platelets / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D005165:Factor V / Q000378:metabolism; D006801:Humans; D013917:Thrombin / Q000096:biosynthesis*; D013925:Thromboplastin / Q000097:blood
D005165:Factor V; D013925:Thromboplastin; D013917:Thrombin