Physiological role of alpha 2-plasmin inhibitor in rats.

For understanding the physiological role of rat alpha 2-plasmin inhibitor (alpha 2-PI), the effect of alpha 2 PI deficiency on the fibrinolytic system was studied in rats in vitro and in vivo. Selective removal of alpha 2 PI from plasma was achieved in vitro and in vivo by immune complex formation with specific anti-rat alpha 2 PI rabbit gamma-globulin and the F(ab')2 fragments derived from specific anti-rat alpha 2 PI rabbit IgG, respectively. Depletion of alpha 2 PI from plasma resulted in almost complete loss of the fast-acting antiplasmin activity of the plasma and in a marked acceleration of urokinase-induced plasma clot lysis. A similar acceleration of thrombus dissolution was also observed, when a thrombus isolated from a thrombosed rat was incubated in alpha 2 PI-deficient serum in vitro. The effect was found to be inversely proportional to the alpha 2 PI levels in plasma or serum. When alpha 2 PI deficiency was induced in rats with experimental venous thrombosis, thrombus size was markedly decreased in association with elevation of serum fibrin degradation products and reduction of plasma plasminogen, indicating enhanced fibrinolysis in vivo. In addition, alpha 2 PI deficiency for a longer period induced a mild bleeding tendency at the sites of venipuncture. These results indicate that alpha 2 PI plays an important role as a stabilizer of fibrin in rats, as in humans.