Urokinase as a Cell Product

Abstract

Fibrin deposition occurs in health and disease. The formation of fibrin results from the sequential activation of proteases according to a scheme now well known as the coagulation cascade. A variety of stimuli can initiate this cascade and the resultant fibrin may be involved in physiological (healing) or pathological (vascular obstruction) sequelae. Resolution of fibrin deposits is accomplished by the action of an enzyme system which has as a substrate the insoluble fibrin polymers. This is the fibrinolytic system and, akin to the coagulation system, consists of sequential activation of proenzymes. Plasminogen, a circulatory ß-globulin, is converted to plasmin (fibrinolysin) by tissue or plasma kinases (activators). One of these activators, urokinase, is produced by renal cells and is excreted in the urine. The teleologically inclined will want to consider that this system maintains the urinary tract free from obstructing fibrin clots. Urokinase has been found therapeutically useful, thus stimulating a search for production sources other than human urine. One successful approach is based on cell culture, thus the inclusion of this topic in your program. I should now like to consider with you the therapeutic use of urokinase, the methods of isolation, and some recent data regarding its function.