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Reactivity of proteinase 3 (PR3) was tested against various amino acid and thioester substrates. The best substrate is Boc-Ala-Ala-Nva-SBzl with a kcat/Km value of 1.0 x 10(6) M-1.s-1. We also studied the effect of C-ANCA on PR3 proteolytic activity towards elastin and inactivation by alpha 1-antitrypsin (alpha 1AT). C-ANCA IgG from 8 patients with active Wegener's granulomatosis were tested and found to inhibit elastin degradation by PR3 and to prevent the inactivation of PR3 by alpha 1AT.

Thrombin has a central regulatory role in hemostasis and is formed by both the intrinsic and extrinsic pathways of blood coagulation (Fenton, 1986, 1981). The major function of this serine protease is the cleavage of fibrinogen to form fibrin clots, but thrombin also activates factors V, VIII, XIII and protein C which are important in the control of hemostasis and thrombosis. In addition, thrombin can stimulate platelet secretion and aggregation in blood, and mediate other nonhemostatic cellular events. Our understanding of the various biological roles of thrombin has been facilitated by the development of convenient chromogenic and fluorogenic assays for the measurement of thrombin activity; and synthetic, low-molecular-weight inhibitors which are important probes for the study of thrombin’s mechanism, specificity, and function in the coagulation system.