PROTEINASES FROM THE FIBRINOLYTIC AND COAGULATION SYSTEMS - ANALYSES OF BINDING TO PREGNANCY ZONE PROTEIN, A PREGNANCY-ASSOCIATED PLASMA PROTEINASE-INHIBITOR

The inhibitory effects of pregnancy zone protein (PZP) on proteinases within the fibrinolytic and coagulation systems have been studied and compared to that of human alpha(2)-macroglobulin (alpha(2)-M). Plasmin, t-PA, urokinase, thrombin, human plasma kallikrein, human and porcine tissue kallikrein were tested for binding to PZP and alpha(2)-M. PZP was cleaved at the 'bait' region as seen in SDS-PAGE, by both human and porcine tissue kallikrein, but not by any of the other proteinases tested and we therefore suggest that PZP may have a role in inhibition of tissue kallikrein. Plasmin, thrombin, and plasma kallikrein were found to be bound and inhibited by alpha(2)-M by cleavage of the 'bait' regions. Minor amounts of cleavage products of alpha(2)-M were detected with t-PA and urokinase after prolonged incubation at room temperature. Cleavage of alpha(2)-M was detected following incubation with porcine tissue kallikrein, but no cleavage was seen following incubation with human tissue kallikrein. The fast inhibition of plasmin, thrombin, and plasma kallikrein suggest that alpha(2)-M may be physiological relevant as an inhibitor for these proteinases. Despite the similarities between alpha(2)-M and PZP, significant differences are observed in the inhibition of proteinases. These results suggest distinctive differences in the function of the two human a-macroglobulins. PZP does only seem to inhibit human tissue kallikrein of the proteinases tested from the fibrinolytic and coagulation systems.