Biological and thrombolytic properties of proenzyme and active forms of human urokinase--I. Fibrinolytic and fibrinogenolytic properties in human plasma in vitro of urokinases obtained from human urine or by recombinant DNA technology.
The fibrinolytic and fibrinogenolytic properties of recombinant pro-urokinase (Rec-pro-UK) and recombinant urokinase (Rec-UK) obtained by expression of the human urokinase cDNA in E. coli, were compared with those of natural urokinase (Nat-UK) of urinary origin and of tissue-type plasminogen activator (t-PA) in a system, composed of a radioactive human plasma clot immersed in citrated human plasma. The specific fibrinolytic effects of Nat-UK, Rec-pro-UK and Rec-UK were very similar, causing significant clot lysis at concentrations of 100 IU/ml plasma or more. t-PA caused equivalent degrees of clot lysis at 10-fold lower concentrations. Activation of the fibrinolytic system in the plasma (fibrinogenolysis), was not observed with t-PA in concentrations which induced complete clot lysis within 5 hr (20-30 IU/ml plasma). With Nat-UK and Rec-UK, all concentrations which caused significant clot lysis (100-200 IU/ml plasma) also caused extensive activation of the plasma fibrinolytic system. With Rec-pro-UK an intermediate response was obtained. The highest amounts required for complete clot lysis in 5 hr (200 IU/ml plasma) also caused significant fibrinogenolysis. At intermediate concentrations (50-100 IU/ml), however, significant clot lysis (40-80%) was observed without systemic fibrinolytic activation.
D004274:DNA, Recombinant; D004792:Enzyme Precursors / Q000302:isolation & purification / Q000502:physiology*; D005340:Fibrinogen / Q000378:metabolism*; D005342:Fibrinolysis; D006801:Humans; D066298:In Vitro Techniques; D014568:Urokinase-Type Plasminogen Activator / Q000302:isolation & purification / Q000502:physiology*
D004274:DNA, Recombinant; D004792:Enzyme Precursors; D005340:Fibrinogen; D014568:Urokinase-Type Plasminogen Activator