ABSTRACT
Plasminogen activators (PAs) are serine proteases, which generate localized proteolysis by converting the zymogen plasminogen to the trypsin-like enzyme plasmin. They play a key role in several regulatory systems such as fibrinolysis, inflammation, pericellular proteolysis, and in cancer metastasis. The importance of PA-inhibitor for measurement of the fibrinolytic system is demonstrated by observations that a low fibrinolytic activity is either due to low PA levels or increased PA-inhibitor. Injection of tissue-type plasminogen activator (t-PA) into rabbits having a high level of PA-inhibitor, induced by the injection of endotoxin, resulted in the same degree of thrombolysis as in rabbits having a low level of PA-inhibitor. PA-inhibitor activity was demonstrated already in the seventies in the conditioned medium of a variety of human tissues, and particularly of endothelial cells and hepatoma cells. In rat granulosa cells PA-inhibitor activity was depressed by treatment with follicle stimulating hormone or luteinizing hormone, possibly due to inhibitor depletion as a consequence of t-PA stimulation.
