Altered distribution of intraglomerular immune complexes in C3-deficient mice.
We have studied the role of complement in a model of glomerular inflammation induced by the in situ formation of immune complexes along the glomerular basement membrane. In C3-deficient mice, produced by homologous recombination, immune complex formation occurs initially in the subendothelial site and progresses slowly to the subepithelial position, whereas wild-type mice do not develop subendothelial deposits. In addition, the accumulation of electron-dense deposits is greater in the complement-deficient mice. Complement therefore influences glomerular handling of immune complexes, possibly because of changes in the physiochemical characteristics of the immune complexes. However, despite evidence of complement activation in the wild-type mice, as demonstrated by immunohistochemical detection of C3, C4 and C9, the degree of proteinuria was similar in C3-deficient mice. We conclude that, although complement is required for the normal glomerular metabolism of immune complexes, other, complement-independent, factors are involved in the generation of glomerular injury in this model.
Sheerin
N S
NS
Department of Renal Medicine and Transplantation, Guy's, King's and St Thomas' Hospitals Medical School, Guy's Campus, London, UK.
Springall
T
T
Carroll
M
M
Sacks
S H
SH
D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D001485:Basement Membrane / Q000276:immunology; D003176:Complement C3 / Q000172:deficiency* / Q000276:immunology; D005260:Female; D005921:Glomerulonephritis / Q000276:immunology* / Q000473:pathology; D007105:Immune Complex Diseases / Q000276:immunology* / Q000473:pathology; D007678:Kidney Glomerulus / Q000276:immunology* / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D011507:Proteinuria / Q000276:immunology; D011817:Rabbits
D000936:Antigen-Antibody Complex; D003176:Complement C3