C3 dependent, C5 independent immune complex glomerulopathy in the mouse.
This study examines the role of complement in a murine model of accelerated nonproliferative immune complex glomerulopathy. Two C5 deficient strains (DBA/2J and B10.D2oSnJ) as well as normocomplementemic mice consistently develop heavy proteinuria and glomeruli show loss of normal visceral epithelial cell architecture within 4 days of intravenous antigen administration. In contrast, animals depleted of C3 with cobra venom factor fail to develop proteinuria and retain discrete foot processes. Semiquantitative evaluation of antigen and antibody in glomeruli shows equivalent deposition in mice from all groups. The localization of these deposits, however, is different in C3-depleted mice. There is extensive accumulation of deposits along the subepithelial aspect of the glomerular basement membrane of normocomplementemic and C5 deficient mice while deposits in glomeruli of C3-depleted animals accumulate in the subendothelial region and do not cross the glomerular basement membrane. These data demonstrate that in this model, glomerular injury is dependent on complement components generated up thru C3 but not C5 or latter components. In addition, our data suggest that C3 is important in the movement of immune complexes across the glomerular basement membrane. Although the mechanism by which complement is mediating injury in this model is not known, it does not appear to involve an inflammatory cell infiltrate or the terminal complement components.
Sawtell
N M
NM
Department of Pathology, University of Cincinnati Medical Center, Ohio.
Hartman
A L
AL
Weiss
M A
MA
Pesce
A J
AJ
Michael
J G
JG
D000818:Animals; D001485:Basement Membrane / Q000648:ultrastructure; D003176:Complement C3 / Q000032:analysis / Q000276:immunology*; D003182:Complement C5 / Q000032:analysis / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D005455:Fluorescent Antibody Technique; D005921:Glomerulonephritis / Q000276:immunology* / Q000473:pathology; D007105:Immune Complex Diseases / Q000276:immunology* / Q000473:pathology; D007678:Kidney Glomerulus / Q000032:analysis / Q000473:pathology / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008854:Microscopy, Electron; D011507:Proteinuria / Q000276:immunology
D003176:Complement C3; D003182:Complement C5