Mechanism of in Vitro Activation of Human Fibrinolytic System: Differential Titration of the Components

¹ From the Enzyme Research Section of the Department of Surgical Physiology, Sloan-Kettering Institute for Cancer Research, and the Department of Biochemistry, Sloan-Kettering Division, Cornell University Medical College, New York City

Treatment of human plasma preparations with varying amounts of streptokinase reveals a maximum proteolytic activity at low streptokinase concentrations and a maximum in fibrinolytic activity (using a bovine plasminogen contaminated substrate) at high streptokinase concentrations. These observations are best explained by the presence in human preparations of a proactivator and a proenzyme. The proactivator, present in large excess, is converted by streptokinase to activator which in turn converts the proenzyme plasminogen to the proteolytic and fibrinolytic enzyme plasmin. A differential titration with streptokinase, using the streptokinase concentration at the appearance of the maximum plateau for proteolytic activity as one end-point, and at the maximum plateau for fibrinolytic activity as the other, reveals relative amounts of the proactivator and the proenzyme.