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 Baker, P. J. Articles by Couser, W. G. Search for Related Content PubMed PubMed Citation Articles by Baker, P. J. Articles by Couser, W. G.

American Journal of Pathology, Vol 135, 185-194, Copyright © 1989 by American Society for Investigative Pathology

REGULAR ARTICLES

Depletion of C6 prevents development of proteinuria in experimental membranous nephropathy in rats

PJ Baker, RF Ochi, M Schulze, RJ Johnson, C Campbell and WG Couser
Department of Medicine, University of Washington, Seattle 98195.

To study the possible role of the complement membrane attack complex, C5b-9, in an experimental rat model that is morphologically indistinguishable from membranous nephropathy in man (passive Heymann nephritis [PHN]), an antibody to rat C6 was used to deplete C6 levels to less than 5% of pretreatment values (C6D) during disease development. C3, C7, C8, and C9 levels were not different in C6D and control rats. After injection of nephritogenic quantities of 125I-anti- Fx1A antibody, the kinetics of disappearance of labeled IgG from the blood were identical in the complement deficient and sufficient groups, and glomerular deposition of 125I-antibody was the same in both groups at 5 days. Glomerular deposits of sheep IgG and C3 were also similar in C6D and controls, but glomerular deposits of C6 and C5b-9 neoantigens were markedly reduced or absent in C6 depleted rats. However, despite equivalent antibody deposits, proteinuria was abolished in C6D rats compared with normocomplementemic controls. Similar results were obtained when F(ab')2 anti-rat C6 IgG was used to deplete C6 during development of PHN. These results demonstrate that C6 is required for the development of the increased glomerular permeability that occurs in PHN, presumably because C6 is required for formation of C5b-9. We conclude that glomerular injury in the PHN model of membranous nephropathy in the rat is mediated by C5b-9.

This article has been cited by other articles:

				S. T. Spicer, G. T. Tran, M. C. Killingsworth, N. Carter, D. A. Power, K. Paizis, R. Boyd, S. J. Hodgkinson, and B. M. Hall Induction of Passive Heymann Nephritis in Complement Component 6-Deficient PVG Rats J. Immunol., July 1, 2007; 179(1): 172 - 178. [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]

				W. G. Couser Membranous Nephropathy: A Long Road but Well Traveled J. Am. Soc. Nephrol., May 1, 2005; 16(5): 1184 - 1187. [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]

				H A Austin and G G Illei Membranous lupus nephritis Lupus, January 1, 2005; 14(1): 65 - 71. [Abstract] [PDF]

				F. Lin, D. J. Salant, H. Meyerson, S. Emancipator, B. P. Morgan, and M. E. Medof Respective Roles of Decay-Accelerating Factor and CD59 in Circumventing Glomerular Injury in Acute Nephrotoxic Serum Nephritis J. Immunol., February 15, 2004; 172(4): 2636 - 2642. [Abstract] [Full Text] [PDF]

				V. Levidiotis, C. Freeman, C. Tikellis, M. E. Cooper, and D. A. Power Heparanase Is Involved in the Pathogenesis of Proteinuria as a Result of Glomerulonephritis J. Am. Soc. Nephrol., January 1, 2004; 15(1): 68 - 78. [Abstract] [Full Text] [PDF]

				D. Turnberg, M. Botto, J. Warren, B. P. Morgan, Mark. J. Walport, and H. T. Cook CD59a Deficiency Exacerbates Accelerated Nephrotoxic Nephritis in Mice J. Am. Soc. Nephrol., September 1, 2003; 14(9): 2271 - 2279. [Abstract] [Full Text] [PDF]

				S. I-H. Hsu and W. G. Couser Chronic Progression of Tubulointerstitial Damage in Proteinuric Renal Disease Is Mediated by Complement Activation: A Therapeutic Role for Complement Inhibitors? J. Am. Soc. Nephrol., July 1, 2003; 14(90002): S186 - 191. [Abstract] [Full Text] [PDF]

				W. G. Couser Complement Inhibitors And Glomerulonephritis: Are We There Yet? J. Am. Soc. Nephrol., March 1, 2003; 14(3): 815 - 818. [Full Text] [PDF]

				A. V. Cybulsky, T. Takano, J. Papillon, A. Khadir, J. Liu, and H. Peng Complement C5b-9 Membrane Attack Complex Increases Expression of Endoplasmic Reticulum Stress Proteins in Glomerular Epithelial Cells J. Biol. Chem., October 25, 2002; 277(44): 41342 - 41351. [Abstract] [Full Text] [PDF]

				S. T. Spicer, H. Ha, R. A. Boyd, X. Y. He, N. Carter, G. Tran, M. J. Penny, S. J. Hodgkinson, and B. M. Hall IL-4 Therapy Prevents the Development of Proteinuria in Active Heymann Nephritis by Inhibition of Tc1 Cells J. Immunol., October 1, 2001; 167(7): 3725 - 3733. [Abstract] [Full Text] [PDF]

				M. G. Robson, H. T. Cook, M. Botto, P. R. Taylor, N. Busso, R. Salvi, C. D. Pusey, M. J. Walport, and K. A. Davies Accelerated Nephrotoxic Nephritis Is Exacerbated in C1q-Deficient Mice J. Immunol., June 1, 2001; 166(11): 6820 - 6828. [Abstract] [Full Text] [PDF]

				B. Schiller, C. He, D. J. Salant, A. Lim, J. J. Alexander, and R. J. Quigg Inhibition of Complement Regulation Is Key to the Pathogenesis of Active Heymann Nephritis J. Exp. Med., October 5, 1998; 188(7): 1353 - 1358. [Abstract] [Full Text] [PDF]

				Y. Lin, M. Vandeputte, and M. Waer Accommodation and T-Independent B Cell Tolerance in Rats With Long Term Surviving Hamster Heart Xenografts J. Immunol., January 1, 1998; 160(1): 369 - 375. [Abstract] [Full Text] [PDF]