EVIDENCE FOR THE REGULATION OF UROKINASE AND TISSUE-TYPE PLASMINOGEN ACTIVATORS BY THE SERPIN, PROTEIN-C INHIBITOR, IN SEMEN AND BLOOD-PLASMA

Since the serine protease inhibitor, protein C inhibitor (PCI), is pre sent in seminal plasma at approximate to 3 mu M, complexes of PCI with urokinase (uPA) and tissue type (tPA) plasminogen activator were quan titated using sandwich enzyme-linked immunosorbent assays (ELISA's). S eminal plasma (N = 10) collected in the absence of extrinsic inhibitor s had a mean of 25 +/- 5 ng/ml uPA:PCI, 76 +/- 23 ng/ml tPA:PCI, and 4 +/- 2 ng/ml of tPA complexes with plasminogen activator inhibitor-1 ( tPA:PAI-1). 93% of the uPA and 17% of the tPA antigen in seminal plasm a was in complex with PCI and, when complexation was inhibited by coll ecting semen into an 1,10-phenanthrolinium solution, 33% of the uPA an d 7% of the tPA was complexed to PCI. Urine (N = 10) contained 4 +/- 1 ng/ml uPA:PCI. In purified system, complexation of uPA and tPA to PCI paralleled the inhibition of the enzymes. In vitro studies in blood a nd seminal plasma showed that heparin stimulated complexation of uPA a nd tPA with PCI, suggesting that negatively charged glycosaminoglycans in blood vessels and in the reproductive system may regulate PCI reac tions with uPA and tPA. These results suggest that PCI is a physiologi c regulator of uPA and tPA in male reproductive tissues and raises que stions about a potential role of PCI in human fertility and in uPA-dep endent cell invasiveness.