Platelet associated u-PA up-regulates u-PA synthesis by endothelial cells.
Adhesion of platelets to endothelium has been shown to induce important changes in endothelial properties. In this study, we examined the effect of platelet-endothelial cell interactions on the expression of urokinase-type plasminogen activator (u-PA) by human microvascular endothelial cells. After incubation of endothelial cells with platelets, a dose-dependent increase in the expression of u-PA Ag was observed and reached a plateau for a ratio of 300 platelets per endothelial cells. The u-PA Ag upregulation resulted from an increase in u-PA mRNA that originated from a synthesis by endothelial cells since no u-PA mRNA was detected in platelets. The platelet-induced u-PA synthesis was inhibited when the endothelial cells were pre-treated with phospholipase C to remove the u-PA receptor, or when the platelets were incubated with an antibody that blocks the binding of u-PA to u-PAR. Taken together, these data indicate that u-PA present on the platelet surface interacts with u-PAR on the endothelial cells and induces the u-PA synthesis. This mechanism may represent a physiological control of platelet-mediated intravascular fibrin deposition.
D000244:Adenosine Diphosphate; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001792:Blood Platelets / Q000737:chemistry* / Q000166:cytology / Q000502:physiology; D002450:Cell Communication; D002460:Cell Line; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D015854:Up-Regulation; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; C524898:PLAUR protein, human; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D000244:Adenosine Diphosphate; D014568:Urokinase-Type Plasminogen Activator