Significance of direct and indirect kinin formation by plasmin in human plasma

Abstract

Human plasma was treated with p-iodobenzoate to inactivate plasmin inhibitors. Incubation of such plasma with streptokinase generated plasmin activity, detectable by caseinolysis. Simultaneously plasma kinin was liberated. Both lima bean inhibitor which specifically inhibits plasmin, and ϵ-amino caproic acid which prevents plasmin activation suppressed the formation of kinin, indicating that plasmin was involved in the streptokinase-induced kinin liberation. Plasma heated to 61° at pH 4 still developed caseinolytic activity upon activation with streptokinase, but no kinin formed. Lima bean inhibitor added to non-heated plasma after treatment with p-iodobenzoate and streptokinase did not block kinin-forming activity. These findings demonstrate that plasmin formed kinin only indirectly by activating a heat labile plasma kininogenase. This enzyme has properties of kininogenase I, equal to classical plasma kallikrein. At concentrations corresponding to those found in iodobenzoate-treated, streptokinase-activated human plasma, purified human plasmin did not liberate kinin from human kininogen I. Only when added at considerably higher concentrations was a direct kinin formation seen. It is concluded that plasmin acts both as a plasma kallikrein activator and as a kininogenase proper. However, under physiological conditions it probably forms kinin only indirectly.