This Article Order Full text via Infotrieve Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Schulze, M. Articles by Couser, W. G. Search for Related Content PubMed PubMed Citation Articles by Schulze, M. Articles by Couser, W. G.

American Journal of Pathology, Vol 142, 179-187, Copyright © 1993 by American Society for Investigative Pathology

REGULAR ARTICLES

Glomerular C3c localization indicates ongoing immune deposit formation and complement activation in experimental glomerulonephritis

M Schulze, CJ Pruchno, M Burns, PJ Baker, RJ Johnson and WG Couser
Division of Nephrology, University of Washington, Seattle 98195.

In antibody-mediated glomerular disease, deposits of C3 (C3b) are common and are degraded by factor I to C3c and C3d. However, the kinetics of C3b degradation in glomerulonephritis have not been defined. To do this, we studied three models of complement-dependent glomerulonephritis with established C3 deposits (passive Heymann nephritis, cationized immunoglobulin G membranous nephropathy, and concanavalin A-anticoncanavalin A glomerulonephritis). C3b deposition was halted by administration of cobra venom factor, and the disappearance of C3c and C3d from glomeruli was measured with specific antibodies and quantitative fluorescence densitometry. Results showed that C3c deposits were reduced by over 85% within 24 hours in all three models. C3c clearance was unaffected by site or mechanism of deposit formation. C3d deposits persisted despite lack of ongoing complement activation. In passive Heymann nephritis when disease activity was monitored by urinary C5b-9 excretion, C3c was cleared in parallel with return of urine C5b-9 excretion to normal values. We conclude that glomerular deposits of C3c are cleared within 24 hours of cessation of complement activation. Positive staining for C3 utilizing antibody specific for the C3c portion documents recent complement activation usually reflecting new immune deposit formation.

This article has been cited by other articles:

				P. Ruggenenti, P. Cravedi, M. C. Sghirlanzoni, E. Gagliardini, S. Conti, F. Gaspari, G. Marchetti, M. Abbate, and G. Remuzzi Effects of Rituximab on Morphofunctional Abnormalities of Membranous Glomerulopathy Clin. J. Am. Soc. Nephrol., November 1, 2008; 3(6): 1652 - 1659. [Abstract] [Full Text] [PDF]

				M. Chen, G.-Q. Xing, F. Yu, G. Liu, and M.-H. Zhao Complement deposition in renal histopathology of patients with ANCA-associated pauci-immune glomerulonephritis Nephrol. Dial. Transplant., October 21, 2008; (2008) gfn586v1. [Abstract] [Full Text] [PDF]

				C. Atkinson, F. Qiao, H. Song, G. S. Gilkeson, and S. Tomlinson Low-Dose Targeted Complement Inhibition Protects against Renal Disease and Other Manifestations of Autoimmune Disease in MRL/lpr Mice J. Immunol., January 15, 2008; 180(2): 1231 - 1238. [Abstract] [Full Text] [PDF]

				A. V. Cybulsky, R. J. Quigg, and D. J. Salant Experimental membranous nephropathy redux Am J Physiol Renal Physiol, October 1, 2005; 289(4): F660 - F671. [Abstract] [Full Text] [PDF]

				P. N. Cunningham and R. J. Quigg Contrasting Roles of Complement Activation and Its Regulation in Membranous Nephropathy J. Am. Soc. Nephrol., May 1, 2005; 16(5): 1214 - 1222. [Abstract] [Full Text] [PDF]

				M. Nangaku, S. J. Shankland, and W. G. Couser Cellular Response to Injury in Membranous Nephropathy J. Am. Soc. Nephrol., May 1, 2005; 16(5): 1195 - 1204. [Abstract] [Full Text] [PDF]

				L. Bao, M. Haas, D. M. Kraus, B. K. Hack, J. K. Rakstang, V. M. Holers, and R. J. Quigg Administration of a Soluble Recombinant Complement C3 Inhibitor Protects Against Renal Disease in MRL/lpr Mice J. Am. Soc. Nephrol., March 1, 2003; 14(3): 670 - 679. [Abstract] [Full Text] [PDF]

				P. PARK, M. HAAS, P. N. CUNNINGHAM, J. J. ALEXANDER, L. BAO, J. M. GUTHRIDGE, D. M. KRAUS, V. M. HOLERS, and R. J. QUIGG Inhibiting the Complement System Does Not Reduce Injury in Renal Ischemia Reperfusion J. Am. Soc. Nephrol., July 1, 2001; 12(7): 1383 - 1390. [Abstract] [Full Text] [PDF]

				C. J. I. RAATS, M. E. LUCA, M. A. H. BAKKER, A. VAN DER WAL, P. HEERINGA, H. VAN GOOR, J. VAN DEN BORN, E. DE HEER, and J. H. M. BERDEN Reduction in Glomerular Heparan Sulfate Correlates with Complement Deposition and Albuminuria in Active Heymann Nephritis J. Am. Soc. Nephrol., August 1, 1999; 10(8): 1689 - 1699. [Abstract] [Full Text]