Evidence for the Occurrence of a Fast-Acting Inhibitor for Tissue-Type Plasminogen Activator in Human Plasma

Human plasma contains a fast-acting t-PA inhibitor, which is not identical with alpha 2-antiplasmin or alpha 2-macroglobulin. The concentration of this inhibitor in normal plasma is highly variable, much lower than that of known plasma protease inhibitors, and in the range of physiologically occurring plasma concentrations of t-PA (0-2 IU/ml). The inhibitor binds to concanavalin A-Sepharose, is rather stable when heated, is not precipitated in euglobulin fractions and probably does not originate from platelets. The inhibitor seems to form a 190 Kd complex with t-PA. The relation between this plasma inhibitor and the recently discovered endothelial cell inhibitor is not yet clear.