Influence of protein C activation on blood coagulation and fibrinolysis in squirrel monkeys.
Protein C is a circulating proenzyme which, upon activation, exerts a potent anticoagulant activity. Infusion of activated bovine protein C into dogs is accompanied by an increase of circulating tissue plasminogen activator (PA) activity. However, the evidence that human protein C shares a similar profibrinolytic capacity is still lacking. Therefore, we investigated the profibrinolytic properties of human protein C in squirrel monkeys (Samiri sciureus). Injection of activated human protein C resulted in prolongation of the activated partial thromboplastin time but was not associated with increased fibrinolytic activity of blood. Similarly, activation of endogenous protein C (up to 20-30%) by infusion of thrombin-thrombomodulin complex markedly reduced blood coagulability without being accompanied by an increase of circulating PA activity. The in vivo-generated anticoagulant activity was identified as activated protein C by the following observations. It was neutralized by rabbit anti-human protein C-IgG, was slowly inhibited by plasma but not by anti-thrombin III, was adsorbable on barium citrate, and expressed amidolytic activity. Activation of protein C appeared to be selective since other parameters such as thrombin time, platelet count, fibrinogen, and factor V levels were unaffected by thrombin-thrombomodulin infusion. Infusion of human plasma derived from whole blood incubated in vitro with human activated protein C also did not induce a fibrinolytic response, suggesting that no second messengers with PA-releasing activity were being generated in blood. It is concluded that in a primate, neither the administration of activated human protein C nor the activation of endogenous protein C are associated with an increase of fibrinolytic activity. These findings question the role of this enzyme in the regulation of PA release in man.
D000818:Animals; D001777:Blood Coagulation; D001779:Blood Coagulation Factors / Q000378:metabolism*; D001835:Body Weight; D004789:Enzyme Activation; D005337:Fibrin / Q000378:metabolism; D005342:Fibrinolysis; D006023:Glycoproteins / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D011486:Protein C; D012453:Saimiri
D001779:Blood Coagulation Factors; D006023:Glycoproteins; D011486:Protein C; D005337:Fibrin