Mechanism of formation of bovine plasminogen activator from human plasmin.

It has been shown that the activation of bovine plasminogen by streptokinase plus a trace amount of human globulin involves a two-stage activation process (1, 2). Ablondi and Hagan (3) proposed that the proactivator of bovine plasminogen was identical with human plasminogen, which became activator by forming complexes with streptokinase. Kline and Fishman (4) using a lysine methyl ester assay demonstrated that the kinetics of inactivation of plasmin was similar to that of proactivator. They stated that plasminogen activator might be formed from plasmin plus streptokinase. The same suggestion was made by Zylber, Blatt, and Jensen (5) and Blatt, Gray, and Jensen (6). However, all these findings did not rule out the possibility that the activator could exist in the form of a plasminogen-streptokinase complex. Recently, Markus and Werkheiser (7,s) postulated the existence of two proactivators in human blood; one (proactivator I) supposedly activated both human and bovine plasminogen while the other (proactivator II) activated bovine plasminogen only. It has also been suggested that both human plasmin and plasminogen could serve as proactivator and form activator with streptokinase (7-9). In the present communication, methods and experiments are presented to elucidate the mechanism of formation of bovine plasminogen activator from human plasmin. It will be shown that human plasmin and not human plasminogen is the immediate precursor of bovine plasminogen activator and is, therefore, the proactivator.