ACTIVATION PATHWAYS OF PLASMINOGEN BY UROKINASE AND TISSUE PLASMINOGEN ACTIVATOR IN THE PLASMA OR CLOTTED PLASMA: COMAPRISON WITH PURIFIED SYSTEMS

Abstract

The activation pathways of a native plasminogen (Glu-plg) were studied in the plasma and purified systems. When purified Glu-plg was activated by urokinase (UK) or tissue plasminogen activator (t-PA), the activation of Glu-plg proceeded very slowly in the presence of fibrinogen, but rapidly in the presence of non crosslinked or cross-linked fibrin. Little formation of modified pig (Lys-plg) was observed in the presence of fibrinogen, but significant amounts of Lys-plg were formed in the presence of fibrin clot. The addition of α2antiplasmin (α2AP) to the mixture of Glu-plg, UK or t-PA, and fibrinogen or fibrin resulted in little formation of Lys-plg in the presence of fibrinogen but significant formation of Lys-plg in the presence of non cross-linked or cross linked fibrin. Alphapantiplasmin did not prevent the formation of Lys-plg from Glu-plg by plasmin in the presence of fibrin regardless of possible cross-linkage of α2AP to fibrin. In contrast to purified system, the activation of Glu-plg by UK or t-PA in the presence of plasma clot resulted in little formation of Lys pig The addition of thrombin and Ca++ to the plasma activated by UK or t-PA resulted in little formation of Lys-plg. These results suggest that Glu-plg was mainly directly activated by UK or t-PA to Glu-plasmin (then Lys-plasmin) in the plasma or plasma clot (non cross-linked or cross-linked), and that some of Glu-plg was converted to Lys-plg by preformed plasmin after UK or t-PA induced activation of Glu-plg in the presence of fibrin. It should be stressed that not all the molecules of Glu-plg were converted to Lys-plg in the presence of fibrin before their activation by activators. Some amounts of Glu-plg were present throughout the activation process in its native form.