Depletion of C6 prevents development of proteinuria in experimental membranous nephropathy in rats.
To study the possible role of the complement membrane attack complex, C5b-9, in an experimental rat model that is morphologically indistinguishable from membranous nephropathy in man (passive Heymann nephritis [PHN]), an antibody to rat C6 was used to deplete C6 levels to less than 5% of pretreatment values (C6D) during disease development. C3, C7, C8, and C9 levels were not different in C6D and control rats. After injection of nephritogenic quantities of 125I-anti-Fx1A antibody, the kinetics of disappearance of labeled IgG from the blood were identical in the complement deficient and sufficient groups, and glomerular deposition of 125I-antibody was the same in both groups at 5 days. Glomerular deposits of sheep IgG and C3 were also similar in C6D and controls, but glomerular deposits of C6 and C5b-9 neoantigens were markedly reduced or absent in C6 depleted rats. However, despite equivalent antibody deposits, proteinuria was abolished in C6D rats compared with normocomplementemic controls. Similar results were obtained when F(ab')2 anti-rat C6 IgG was used to deplete C6 during development of PHN. These results demonstrate that C6 is required for the development of the increased glomerular permeability that occurs in PHN, presumably because C6 is required for formation of C5b-9. We conclude that glomerular injury in the PHN model of membranous nephropathy in the rat is mediated by C5b-9.
Baker
P J
PJ
Department of Medicine, University of Washington, Seattle 98195.
Ochi
R F
RF
Schulze
M
M
Johnson
R J
RJ
Campbell
C
C
Couser
W G
WG
D000818:Animals; D001666:Binding Sites, Antibody; D015153:Blotting, Western; D003176:Complement C3 / Q000032:analysis; D003183:Complement C6 / Q000302:isolation & purification / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D015433:Glomerulonephritis, Membranous / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D011507:Proteinuria / Q000517:prevention & control*; D051381:Rats; D011919:Rats, Inbred Strains
D003176:Complement C3; D003183:Complement C6; D007074:Immunoglobulin G