Role of the terminal complement pathway in accelerated autologous anti-glomerular basement membrane nephritis.

The terminal complement pathway (C5b to C9) has been demonstrated to have an important role in the mediation of glomerular immune injury in various models of experimental glomerulonephritis. In the present studies, the role of the terminal complement pathway in the accelerated autologous phase of anti-glomerular basement membrane (GBM) nephritis in the rabbit was investigated. Normocomplementemic rabbits and rabbits deficient in C6 (C6D) who are therefore unable to form the terminal complement pathway were immunized with sheep immunoglobulin G (IgG) before being injected with a subnephrotoxic dose of the gamma 2 fraction of sheep anti-rabbit GBM. C6D animals had a delay in the onset of the glomerular injury, as manifested by proteinuria. At 72 hours, controls had a greater degree of proteinuria (15.2 +/- 8.8 mg protein/mg creatinine vs. 2.6 +/- 2.1, P = 0.197), but at 120 hours there were no differences in proteinuria between C6D and control animals (11.1 +/- 3.6 mg protein/mg creatinine vs. 12.2 +/- 6.2, P = 0.89). Light microscopy demonstrated more severe glomerular injury in C6D animals with marked cellular proliferation and large areas of glomerular necrosis. Interestingly, C6D animals had significantly higher levels of sheep IgG remaining in their glomeruli at 120 hours (0.95 +/- 0.12 micrograms sheep IgG/1 x 10(4) glomeruli, N = 11, vs. 0.57 +/- 0.07, N = 11, P = 0.014) and 72 hours (1.22 +/- 0.25 micrograms, N = 3, vs. 0.60 +/- 0.15, N = 3, P = 0.104) compared with 24 hours when there was no difference (1.25 +/- 0.22 micrograms, N = 7, vs. 1.08 +/- 0.14, N = 7, P = 0.53). C6D rabbits had a greater rise in serum creatinine at 120 hours (2.3 +/- 0.5 mg/dl vs. 1.3 +/- 6.4, P = 0.132). We conclude that in C6D animals, the persistence of glomerular immune deposits is responsible for more severe renal injury and renal failure.
AuthorsG C Groggel, D A Terreros
JournalThe American journal of pathology (Am J Pathol) Vol. 136 Issue 3 Pg. 533-40 (Mar 1990) ISSN: 0002-9440 [Print] UNITED STATES
PMID2180310 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Complement C6
  • Immunoglobulin G
  • Creatine
  • Animals
  • Basement Membrane (physiopathology, ultrastructure)
  • Complement Activation (physiology)
  • Complement C6 (physiology)
  • Complement Pathway, Classical (physiology)
  • Creatine (urine)
  • Disease Models, Animal
  • Fluorescent Antibody Technique
  • Immunoglobulin G (analysis)
  • Kidney Glomerulus (pathology, physiopathology, ultrastructure)
  • Nephritis (metabolism, pathology, physiopathology)
  • Proteinuria (metabolism)
  • Rabbits

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