The relative inhibition by α 2-antiplasmin and plasminogen activator inhibitor-1 of clot lysis in vitro

Abstract

This report describes an investigation into the relative importance of two major inhibitors of the fibrinolytic system, α2-antiplasmin (α2-AP) and type 1 plasminogen activator inhibitor (PAI-1), on the expression of fibrinolysis in vitro. By using both human PAI-1-rich plasma and endotoxin-induced PAI-1-rich rabbit plasma, it was demonstrated that the t-PA/PAI-1 complexes are quite active on the fibrin/plasminogen moeity derived froml the corresponding euglobulin fraction (which retained approximately (60% of the PAI-I activity, but lacked α2-AP which is totally removed in the supernatant of this fraction). By using PAI-1-rich plasma, PAI-1-rich euglobulin fraction derived from this plasma and α2-AP-depleted PAI-1-rich plasma, it was demonstrated that exogenous t-PA-mediated lysis of 125I fibrin clots is significantly inhibited by the α2-AP in the surrounding medium and the α2-AP crosslinked to fibrin, whereas no inhibitory role was evident over a wide concentration range of PAI-1 in the surrounding fluid. In the more dynamic state in which all components are present during the endogenous t-PA-mediated formation and lysis of plasma clots (as assessed in a spectrophotometer at 350nm), it was observed that PAI-1 plays no role in the inhibition of lysis of rapidly forming fibrin. The spectrophotometric profile of α2-AP-depleted PAI-1-rich plasma clot lysis could be returned to that of the control PAI-1-rich plasma by the addition of α2-AP alone. The addition of the cellular fraction of blood did not significantly alter these observations. These results suggest that the inhibitor of major physiological importance in the fluid phase of blood is α2-AP, operating both at the surface of forming fibrin and in the circulation, while PAI-1 seems to play no obvious role.