Inhibition of the human tissue plasminogen activator in plasma from different species

The rate and extent of complex formation between protease inhibitors present in plasma from different species and a human plasminogen activator purified to homogeneity from the supernatant of a human melanoma cell line was studied in vitro. The fibrinolytic activity of the one-chain plasminogen activator disappeared from human, cat and rabbit plasma with a half-life of 100 minutes. By means of antibodies directed against purified protease inhibitors the main inhibitor in human, cat, dog and rabbit plasma was identified as ₂-antiplasmin. ₂-macroglobulin and Cl-esterase-inhibitor functioned as inhibitors to a lesser extent. The main inhibitor in rat plasma was ₂-macroglobulin. The plasma half-life was 3 (rabbit and human) to 10 (dog and rat) times shorter for the two-chain form than for the one-chain form of the plasminogen activator molecule. It is also concluded that, with respect to plasma elimination of the fibrinolytic activity, among the common laboratory animals, the rabbit is the most suitable animal available for the study of fibrinolysis.