The Interaction of Streptokinase with Plasminogen

Abstract

bovine plasminogen, an ability possessed by neither of the two components alone, has been the basis of the hypothesis that solutions of human plasminogen contain a “proactivator” which, when combined with streptokinase, is capable of activating bovine plasminogen. It was tacitly assumed that the same “activator” was also responsible for the catalytic conversion of human plasminogen when the latter was mixed with streptokinase. The nature of proactivator and its presumed streptokinase complex was for some time a controversial subject in the field, some workers maintaining that proactivator was a separate molecular species distinct from plasminogen (l-3) and others that it was identical with plasminogen or with plasmin (4, 5). In experiments with the use of column chromatography for the fractionation of human plasminogen, proactivator activity invariably was eluted together with plasminogen activity (6, 7). It is important to note that in all these experiments activator activity was tested on bovine plasminogen. In a recent paper, Kline and Fishman (8) convincingly demonstrated that the catalyst responsible for the activation of bovine plasminogen was a human plasmin-streptokinase complex, and thus defined human plasmin as the proactivator for this function. Our experiments have independently led us to the same conclusion (9). In the course of our studies, however, it became evident that the activator responsible for the activation of human plasminogen by streptokinase cannot be identical with the complex operative in the conversion of bovine plasminogen. The agent (Activator I) which catalyzes the conversion of human plasminogen appears to be a complex between streptokinase and Proactivator I, a substance present in variable amounts in solutions of human plasminogen. The present paper analyzes the rates of development of plasmin and of Activator II activity and discusses the nature of Activator I. A method for the quantitative estimation of Proactivator I is presented.