The Enhancement of Chloroform-Induced Plasma Proteolytic Activity by Epsilon Aminocaproic Acid

Abstract

Proteolytic activity develops in human plasma treated with streptokinase (1), urokinase (2, 3), tissue particles or extracts (4, 5) or chloroform (6). The protease which evolves in each case has been referred to by the generic name, plasmin, and seems to be derived from the same proenzyme, plasminogen (7-10). The activation of plasminogen by streptokinase, urokinase and tissue extracts may be significantly inhibited by epsilon aminocaproic acid (11,12). The effect of this substance upon the activation of plasminogen by chloroform has not been reported.The present study is concerned with the effect of epsilon aminocaproic acid upon the development of proteolytic activity in chloroform-treated euglobulin fractions of human plasma. Epsilon aminocaproic acid not only failed to impede but actually enhanced the development of proteolytic activity, as measured upon a substrate of casein. Although fibrinolytic activity was also enhanced, this could be demonstrated only if the chloroform-treated euglobulin was first freed of epsilon aminocaproic acid by dialysis. The techniques described, then, permit the preparation of plasmin of high proteolytic activity, yet readily separated from the activating agents. The implications of these observations will be discussed; our studies have not provided an adequate explanation for this unexpected effect of epsilon aminocaproic acid. Nomenclature, Materials and MethodsPl~min (or fibrinolysin) designates the one or several enzymes of plasma which can digest fibrinogen, fibrin, casein and certain other proteins at or near neutrality. It exists in plasma in the form of an inactive precursor, plasminogen (or profibrinolysin). Plasminogen can be activated by streptokinase (a principle found in filtrates of cultures of certain beta hemolytic streptococci) (1), uroldnase (a substance found in normal urine) (2, 3), tissue particles (4,5)