Protection against anti-glomerular basement membrane (GBM)-mediated nephritis in C3- and C4-deficient mice

Clin Exp Immunol. 1997 Dec;110(3):403-9. doi: 10.1046/j.1365-2249.1997.4261438.x.


Mice rendered completely deficient of the complement components C3 or C4 were used to determine the influence of complement activation in the heterologous phase of the anti-GBM disease model. In wild-type animals the disease is characterized by a neutrophil infiltrate, capillary thrombosis, proteinuria and C3 and C4 deposited within the glomerulus. The early infiltration of neutrophils into the glomeruli is greater in wild-type mice (2.8 +/- 0.3) compared with C3-deficient (1.4 +/- 0.2) and C4-deficient (1.2 +/- 0.003) mice. Deficiency also protects against the subsequent development of proteinuria (2.99 +/- 1.11 mg/24h, 0.059 mg/24h and 0.327 +/- 0.14 mg/24h in wild-type, C3-deficient and C4-deficient mice, respectively) and decreases glomerular capillary thrombosis in both C3- and C4-deficient mice. The degree of protection is greater in the C3-deficient than the C4-deficient animals, suggesting both classical and alternative pathway involvement. These studies support a critical role for complement in the development of anti-GBM disease. However, the protective effect of complement deficiency can be broken if the dose of nephritogenic antibody is increased.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albuminuria / etiology
  • Animals
  • Basement Membrane / immunology
  • Complement C3 / deficiency
  • Complement C3 / physiology*
  • Complement C4 / deficiency
  • Complement C4 / physiology*
  • Female
  • Glomerulonephritis / prevention & control*
  • Immunohistochemistry
  • Kidney Glomerulus / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Neutrophils / physiology
  • Rabbits
  • Serum Albumin / analysis
  • Thrombosis / etiology


  • Complement C3
  • Complement C4
  • Serum Albumin