Summary

The cornerstone of hemostasis is the ability of the organism tolimit the enzymatic processes involved, thereby avoiding thrombosis.For this, anticoagulant systems in place involve serpins,such as PAI-1 and antithrombin III, which bind to their targetedserine proteases and limit their period of activity.We have previouslyidentified the serine protease furin as a platelet-derivedenzyme with an intrinsic role in platelet functions.We now reportthat furin enzymatic activity decreased rapidly followingplatelet activation,corresponding with the increase in formationof a high 180 M r SDS-stable complex composed of furin and the PI8 serpin.PI8 is shown to be a platelet-derived constituent,synthesizedby megakaryocytes and stored in platelets prior to itsrelease. Immunoprecipitation and purification of the PI8-furincomplex confirmed their direct interaction and indicates thatone of the roles of PI8 is to inhibit furin enzymatic activity. Furthermore,our findings demonstrate the inhibitory capacity ofexogenous PI8 in platelet aggregation assays.The finding that PI8is released by platelets and controls functional responses suggestsa role for this serpin in platelet-regulated pathophysiologicalresponses.