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) may be due to plasmin-induced platelet aggregation. t-PA caused platelet aggregation by conversion of plasminogen to plasmin under certain conditions. 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 process. The action of plasmin was inhibited by large thrombin antagonistic molecules such as argatroban-inactivated thrombin or anti-thrombin receptor peptide antibodies but not by small molecules like thrombin receptor antagonist peptides. This suggests that target molecules of plasmin on the surface of platelets may not be thrombin receptors but may exist 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) monoclonal antibodies suggested that plasmin might bind to platelets through the N-terminal region. The binding of plasmin to platelets was suppressed by aprotinin and EACA, furthermore indicating that protease catalytic sites and lysine binding regions are involved in interaction of plasmin to platelet.
Watabe
A
A
Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, Tokyo, Japan.
Ohta
M
M
Matsuyama
N
N
Mizuno
K
K
el Borai
N
N
Tanimoto
T
T
Kawanishi
T
T
Hayakawa
T
T
D015119:Aminocaproic Acid / Q000494:pharmacology; D007611:Aprotinin / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism / Q000494:pharmacology*; D006629:Hirudins / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D009930:Organic Chemicals; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000494:pharmacology
D006629:Hirudins; D009930:Organic Chemicals; D010975:Platelet Aggregation Inhibitors; D011480:Protease Inhibitors; D015842:Serine Proteinase Inhibitors; C107927:bdellin; D007611:Aprotinin; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D015119:Aminocaproic Acid