A new function for activated protein C: activated protein C prevents inhibition of plasminogen activators by releasate from mononuclear leukocytes--platelet suspensions stimulated by phorbol diester.
Mononuclear leukocytes release an inhibitor of plasminogen activators. Mononuclear leukocyte mixtures (400 to 1,000/mm3) lysed fibrin (8.3 microM) clots in the presence of plasminogen (0.58 microM). Anti-urokinase IgG (0.16 microM) inhibited this fibrinolysis. 2-Deoxyglucose (5 mM) and oligomycin (2.3 microM) also inhibited fibrinolysis. Incubation of mononuclear leukocytes (3,200/microliter) with phorbol-12 myristate 13-acetate (20 nM) for ten minutes at 37 degrees C aggregated the monocyte and platelet components and inhibited fibrinolysis. The releasate from these stimulated cells in dilutions ranging from undiluted to 1:16 inhibited urokinase (1.6 pM) and tissue plasminogen activator (1.4 pM). This releasate did not inhibit plasmin (2.5 nM). Incubation of this releasate with activated protein C (33 nM to 333 nM) for ten minutes at 37 degrees C before addition of either urokinase, or tissue plasminogen activator and plasminogen completely prevented this inhibition. Thrombin, factor Xa, DIP-activated protein C had no affect on this inhibition. We conclude that activated protein C facilitates fibrinolysis by preventing inhibition of plasminogen activators. This may be a mechanism by which activated protein C increases fibrinolytic activity in vivo.
D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D005342:Fibrinolysis / Q000187:drug effects; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007962:Leukocytes / Q000502:physiology*; D009000:Monocytes / Q000502:physiology; D010704:Phorbols / Q000494:pharmacology*; D010960:Plasminogen Activators / Q000037:antagonists & inhibitors*; D015849:Plasminogen Inactivators; D011486:Protein C; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013917:Thrombin / Q000494:pharmacology; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology
D006023:Glycoproteins; D010704:Phorbols; D015849:Plasminogen Inactivators; D011486:Protein C; D010960:Plasminogen Activators; D013917:Thrombin; D014568:Urokinase-Type Plasminogen Activator; D013755:Tetradecanoylphorbol Acetate