INVOLVEMENT OF PROTEASE INHIBITORS IN STAPHYLOKINASE-INDUCED FIBRIN-SPECIFIC FIBRINOLYSIS

We compared the fibrinolytic properties of recombinant staphylokinase (SAK), a fibrin-specific plasminogen activator, with those of streptok inase and tissue-type plasminogen activator (t-PA) by means of the ami dolytic method. We also investigated the involvement of alpha(2)-macro globulin, C-1-inactivator and alpha(1)-antitrypsin in SAK-induced fibr in-specific fibrinolysis. Both SAK and t-PA activated plasminogen effi ciently in the presence of fibrin in human plasma. Although t-PA activ ated plasminogen dependently on fibrin in the reconstituted plasma sys tem, SAK activated plasminogen independently of fibrin without alpha(2 )-plasmin inhibitor (alpha(2)-antiplasmin, alpha(2)-PI). These finding s suggest that fibrin and alpha(2)-PI play important roles in plasmino gen activation by SAK but not by t-PA. Furthermore, protease inhibitor s such as alpha(2)-PI, alpha(2)-macroglobulin, C-1-inactivator and alp ha(1)-antitrypsin inhibited plasminogen activation by SAK and the inhi bitory actions of these protease inhibitors disappeared in the presenc e of fibrin. This shows that alpha(2)-macroglobulin, C-1-inactivator a nd alpha(1)-antitrypsin, other than alpha(2)-PI, contribute to the fib rin-specificity of SAK.