CHARACTERIZATION OF PLASMIN-INDUCED PLATELET-AGGREGATION

This study was undertaken to determine if reocclusion after treatment of myocardial infarction with a tissue-plasminogen activator (t-PA) ma y be due to plasmin-induced platelet aggregation. t-PA caused platelet aggregation by conversion of plasminogen to plasmin under certain con ditions. Plasmin-induced platelet aggregation was inhibited by serine protease inhibitors, aprotinin and bdellin, and a lysine binding site inhibitor, epsilon-aminocaproic acid (EACA). Extracellular [Ca2+], and RGDS sequence-dependent steps were involved in the aggregation proces s. The action of plasmin was inhibited by large thrombin antagonistic molecules such as argatroban-inactivated thrombin or anti-thrombin rec eptor peptide antibodies but not by small molecules like thrombin rece ptor antagonist peptides. This suggests that target molecules of plasm in on the surface of platelets may not be thrombin receptors but may e xist very close to thrombin receptors. Binding experiments using FITC- labeled plasmin showed that plasmin has its binding sites on platelets . Flow cytometric analyses with four types of anti-plasmin(ogen) monoc lonal antibodies suggested that plasmin might bind to platelets throug h the N-terminal region. The binding of plasmin to platelets was suppr essed by aprotinin and EACA furthermore indicating that protease catal ytic sites and lysine binding regions are involved in interaction of p lasmin to platelet.