Protection against anti-glomerular basement membrane (GBM)-mediated nephritis in C3- and C4-deficient mice.
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.
Sheerin
N S
NS
Department of Nephrology and Transplantation, Guy's Hospital, UMDS, London, UK.
Springall
T
T
Carroll
M C
MC
Hartley
B
B
Sacks
S H
SH
D000419:Albuminuria / Q000209:etiology; D000818:Animals; D001485:Basement Membrane / Q000276:immunology; D003176:Complement C3 / Q000172:deficiency / Q000502:physiology*; D003181:Complement C4 / Q000172:deficiency / Q000502:physiology*; D005260:Female; D005921:Glomerulonephritis / Q000517:prevention & control*; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000502:physiology; D011817:Rabbits; D012709:Serum Albumin / Q000032:analysis; D013927:Thrombosis / Q000209:etiology
D003176:Complement C3; D003181:Complement C4; D012709:Serum Albumin