Logo of amjpatholAmerican Journal of Pathology For AuthorsAmerican Journal of Pathology SubscribeAmerican Journal of Pathology SearchAmerican Journal of Pathology Current IssueAmerican Journal of Pathology About the JournalAmerican Journal of Pathology
Am J Pathol. Jan 1993; 142(1): 179–187.
PMCID: PMC1886837

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


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.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (2.3M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Couser WG. Mediation of immune glomerular injury. J Am Soc Nephrol. 1990 Jul;1(1):13–29. [PubMed]
  • Couser WG, Baker PJ, Adler S. Complement and the direct mediation of immune glomerular injury: a new perspective. Kidney Int. 1985 Dec;28(6):879–890. [PubMed]
  • Tack BF. The beta-Cys-gamma-Glu thiolester bond in human C3, C4, and alpha 2-macroglobulin. Springer Semin Immunopathol. 1983;6(4):259–282. [PubMed]
  • Mollnes TE, Lachmann PJ. Regulation of complement. Scand J Immunol. 1988 Feb;27(2):127–142. [PubMed]
  • Pangburn MK, Müller-Eberhard HJ. The C3 convertase of the alternative pathway of human complement. Enzymic properties of the bimolecular proteinase. Biochem J. 1986 May 1;235(3):723–730. [PMC free article] [PubMed]
  • Schulze M, Baker PJ, Perkinson DT, Johnson RJ, Ochi RF, Stahl RA, Couser WG. Increased urinary excretion of C5b-9 distinguishes passive Heymann nephritis in the rat. Kidney Int. 1989 Jan;35(1):60–68. [PubMed]
  • Pruchno CJ, Burns MW, Schulze M, Johnson RJ, Baker PJ, Couser WG. Urinary excretion of C5b-9 reflects disease activity in passive Heymann nephritis. Kidney Int. 1989 Jul;36(1):65–71. [PubMed]
  • Pruchno CJ, Burns MM, Schulze M, Johnson RJ, Baker PJ, Alpers CE, Couser WG. Urinary excretion of the C5b-9 membrane attack complex of complement is a marker of immune disease activity in autologous immune complex nephritis. Am J Pathol. 1991 Jan;138(1):203–211. [PMC free article] [PubMed]
  • Salant DJ, Darby C, Couser WG. Experimental membranous glomerulonephritis in rats. Quantitative studies of glomerular immune deposit formation in isolated glomeruli and whole animals. J Clin Invest. 1980 Jul;66(1):71–81. [PMC free article] [PubMed]
  • Couser WG, Ochi RF, Baker PJ, Schulze M, Campbell C, Johnson RJ. C6 depletion reduces proteinuria in experimental nephropathy induced by a nonglomerular antigen. J Am Soc Nephrol. 1991 Oct;2(4):894–901. [PubMed]
  • Johnson RJ, Klebanoff SJ, Ochi RF, Adler S, Baker P, Sparks L, Couser WG. Participation of the myeloperoxidase-H2O2-halide system in immune complex nephritis. Kidney Int. 1987 Sep;32(3):342–349. [PubMed]
  • Mancini G, Carbonara AO, Heremans JF. Immunochemical quantitation of antigens by single radial immunodiffusion. Immunochemistry. 1965 Sep;2(3):235–254. [PubMed]
  • Quigg RJ, Cybulsky AV, Salant DJ. Effect of nephritogenic antibody on complement regulation in cultured rat glomerular epithelial cells. J Immunol. 1991 Aug 1;147(3):838–845. [PubMed]
  • Baker PJ, Adler S, Yang Y, Couser WG. Complement activation by heat-killed human kidney cells: formation, activity, and stabilization of cell-bound C3 convertases. J Immunol. 1984 Aug;133(2):877–881. [PubMed]
  • Kerjaschki D, Schulze M, Binder S, Kain R, Ojha PP, Susani M, Horvat R, Baker PJ, Couser WG. Transcellular transport and membrane insertion of the C5b-9 membrane attack complex of complement by glomerular epithelial cells in experimental membranous nephropathy. J Immunol. 1989 Jul 15;143(2):546–552. [PubMed]
  • Jepsen HH, Teisner B, Folkersen J, Svehag SE. Enhancing effect of autologous human erythrocytes on generation of C3 cleavage products beyond iC3b. Complement. 1988;5(3):120–129. [PubMed]
  • Vedeler CA, Matre R, Iversen BM. Glomerular CR1 express in situ cofactor activity for degradation of C3b. Int Arch Allergy Appl Immunol. 1990;92(1):60–63. [PubMed]
  • Kazatchkine MD, Fearon DT, Appay MD, Mandet C, Bariety J. Immunohistochemical study of the human glomerular C3b receptor in normal kidney and in seventy-five cases of renal diseases: loss of C3b receptor antigen in focal hyalinosis and in proliferative nephritis of systemic lupus erythematosus. J Clin Invest. 1982 Apr;69(4):900–912. [PMC free article] [PubMed]
  • Fischer E, Appay MD, Cook J, Kazatchkine MD. Characterization of the human glomerular C3 receptor as the C3b/C4b complement type one (CR1) receptor. J Immunol. 1986 Feb 15;136(4):1373–1377. [PubMed]
  • Kasinath BS, Maaba MR, Schwartz MM, Lewis EJ. Demonstration and characterization of C3 receptors on rat glomerular epithelial cells. Kidney Int. 1986 Dec;30(6):852–861. [PubMed]
  • Foidart JB, Dechenne CA, Mahieu P, Creutz CE, de Mey J. Tissue culture of normal rat glomeruli. Isolation and morphological characterization of two homogeneous cell lines. Invest Cell Pathol. 1979 Jan-Mar;2(1):15–26. [PubMed]
  • Makker SP, Kanalas JJ. Course of transplanted Heymann nephritis kidney in normal host. Implications for mechanism of proteinuria in membranous glomerulonephropathy. J Immunol. 1989 May 15;142(10):3406–3410. [PubMed]
  • Schulze M, Donadio JV, Jr, Pruchno CJ, Baker PJ, Johnson RJ, Stahl RA, Watkins S, Martin DC, Wurzner R, Gotze O, et al. Elevated urinary excretion of the C5b-9 complex in membranous nephropathy. Kidney Int. 1991 Sep;40(3):533–538. [PubMed]
  • Brenchley PE, Coupes B, Short CD, O'Donoghue DJ, Ballardie FW, Mallick NP. Urinary C3dg and C5b-9 indicate active immune disease in human membranous nephropathy. Kidney Int. 1992 Apr;41(4):933–937. [PubMed]
  • Doi T, Kanatsu K, Nagai H, Suehiro F, Kuwahara T, Hamashima Y. Demonstration of C3d deposits in membranous nephropathy. Nephron. 1984;37(4):232–235. [PubMed]
  • Kusunoki Y, Itami N, Tochimaru H, Takekoshi Y, Nagasawa S, Yoshiki T. Glomerular deposition of C4 cleavage fragment (C4d) and C4-binding protein in idiopathic membranous glomerulonephritis. Nephron. 1989;51(1):17–19. [PubMed]
  • Jennette JC, Iskandar SS, Dalldorf FG. Pathologic differentiation between lupus and nonlupus membranous glomerulopathy. Kidney Int. 1983 Sep;24(3):377–385. [PubMed]
  • Pierides AM, Malasit P, Morley AR, Willkinson R, Uldall PR, Kerr DN. Idiopathic membranous nephropathy. Q J Med. 1977 Apr;46(182):163–177. [PubMed]
  • Med M. Prenatal development of thoracic intervertebral articulation. Folia Morphol (Praha) 1977;25(2):175–177. [PubMed]
  • Roberts JL, Wyatt RJ, Schwartz MM, Lewis EJ. Differential characteristics of immune-bound antibodies in diffuse proliferative and membranous forms of lupus glomerulonephritis. Clin Immunol Immunopathol. 1983 Nov;29(2):223–241. [PubMed]
  • Rauterberg EW, Lieberknecht HM, Wingen AM, Ritz E. Complement membrane attack (MAC) in idiopathic IgA-glomerulonephritis. Kidney Int. 1987 Mar;31(3):820–829. [PubMed]
  • Emancipator SN, Ovary Z, Lamm ME. The role of mesangial complement in the hematuria of experimental IgA nephropathy. Lab Invest. 1987 Sep;57(3):269–276. [PubMed]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Compound
    PubChem Compound links
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...