A PREALBUMIN ACTIVATOR OF PREKALLIKREIN II. DERIVATION OF ACTIVATORS OF PREKALLIKREIN FROM ACTIVE HAGEMAN FACTOR BY DIGESTION WITtt

Bradykinin is generated in human plasma by the action of plasma kallikrein upon kininogen (1, 2). Although Hageman factor is required for the formation of kallikrein (3, 4), the role of Hageman factor in the formation of the prekallikrein activator is not clearly delineated. Kaplan and Austen (5) have described a prekallikrein activator present in human serum which has a prealbumin mobility on disc gel electrophoresis, an estimated molecular weight of 35,000 by Sephadex G-100 filtration (Pharmacia Fine Chemicals Inc., Uppsala, Sweden), and the capacity to correct selectively the coagulation defect of Hageman factor-deficient plasma. Prolonged dialysis of a partially purified preparation of active Hageman factor resulted in the development of prealbumin bands in the position previously noted for the prekallikrein activator derived from serum; the eluates of these bands had prekallikrein-activating activity and corrected Hageman factor deficiency. I t was therefore postulated that active Hageman factor dissociates into fragments which retain clot-promoting activity while manifesting a striking ability to activate prekallikrein (5). Since plasminogen was recognized in preparations of highly purified Hageman factor (6), and since plasmin has been implicated in the activation of prekallikrein (7), it seemed possible that plasmin was responsible for the development of prekallikrein-activating activity from active Hageman factor. The cleavage of active Hageman factor by streptokinase-activated, highly purified plasminogen to form the prekallikrein activator is described herein.