Summary
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 k cat/ K m value of 1.0 × 106 M−1.s−1. We also studied the effect of C-ANCA on PR3 proteolytic activity towards elastin and inactivation by alphas-antitrypsin (α1AT). 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 α1AT.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Kao, R.C., Wehner, N.G., Skubitz, K.M., Gray, B.H., and Hoidal, J.R., 1988, Proteinase 3. A distinct human polymorphonuclear leukocyte proteinase that produces emphysema in hamsters. JCIin.Invest. 82: 1963–1973.
Campanelli, D., Melchior, M., Fu, Y., Nakata, M., Shuman, H., Nathan, C.F., and Gabay, J.E., 1990, Cloning of cDNA for proteinase 3: a serine protease, antibiotic, and autoantigen from human neutrophils. J.Exp.Med. 72: 1709–1715.
Rao, N.V., Wehner, N.G., Marshall, B.C., Gray, W.R., Gray, B.H., and Hoidal, J.R., 1991, Characterization of proteinase 3 (PR3), a neutrophil serine proteinase. Structural and functional properties. J.Biol.Chem. 266: 9540–9548.
Goldschmeding, R., van der Schoot, C.E., ten Bokkel Huinink, D., Hack, C.E., van den Ende, M., Kallenberg, C.G.M., and von dem Borne, A.E.G.Kr., 1989, Wegener’s granulomatosis autoantibodies identify a novel diisopropyl-fluorophosphate-binding protein in the lysosomes of normal human neutrophils. J.Chn.Invest. 84: 1577–1587.
Kallenberg, C.G.M., Cohen Tervaert, J.W., van der Woude, F.J., Goldschmeding, R., von dem Borne, A.E.G.Kr., and Weening, J.J., 1991, Autoimmunity to lysosomal enzymes: new clues to vasculitis andglomerulonephritis? Immunol. Today 12: 61–64.
Falk, R.J., Terre, R.S., Charles, L.A., and Jennette, J.C., 1990, Anti-neutrophil cytoplasmic autoantibodies induce neutrophils to degranulate and produce oxygen radicals in vitro. Proc.Natl.Acad.Sci. USA 87: 4115–4119.
Kam, C-M., Kerrigan, J.E., Dolman, K.M., Goldschmeding, R., von dem Borne, A.E.G.Kr., and Powers, J.C., 1992, Substrate and inhibitor studies on proteinase 3. FEBS-Letters 297: 119–123.
Campanelli, D., Detmers, P.A., Nathan, C.F., and Gabay, J.E., 1990, Azurocidin and a homologous serine protease from neutrophils. Differential antimicrobial and proteolytic properties. J. Clin.In vest. 85: 904–915.
Nuijens, J.H., Abbink, J.J., Wachtfogel, Y.T., Colman, R.W., Eerenberg, A.J.M., Dors, D., Kamp, A.M., Strack van Schijndel, R.J.M., Thijs, L.G., and Hack, C.E., Plasma elastase-a lantitrypsin and lactoferrin in sepsis: evidence for neutrophils as mediators in fatal sepsis. J. Lab.Clin.Med. 119: 159–168.
Weiss, S.J., 1989, Tissue destruction by neutrophils. NEng1J.Med 320: 365–376.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1993 Springer Science+Business Media New York
About this chapter
Cite this chapter
Dolman, K.M. et al. (1993). Proteinase 3: Substrate Specificity and Possible Pathogenetic Effect of Wegener’s Granulomatosis Autoantibodies (C-ANCA) by Dysregulation of the Enzyme. In: Gross, W.L. (eds) ANCA-Associated Vasculitides. Advances in Experimental Medicine and Biology, vol 336. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9182-2_7
Download citation
DOI: https://doi.org/10.1007/978-1-4757-9182-2_7
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4757-9184-6
Online ISBN: 978-1-4757-9182-2
eBook Packages: Springer Book Archive