C6 depletion reduces proteinuria in experimental nephropathy induced by a nonglomerular antigen.
The role of the complement membrane attack complex, C5b-9, in mediating glomerular injury has been well defined in models of membranous nephropathy induced by antibody to endogenous glomerular epithelial cell membrane antigens. The effect of selective C6 depletion (to prevent C5b-9 formation) on morphologic characteristics and proteinuria in a model of in situ subepithelial immune complex nephritis induced by an exogenous cationized antigen (human immunoglobulin G (IgG)) followed by rabbit antibody to human IgG was studied. Selective C6 depletion was achieved by repeated administration of a goat antibody to rat C6. Other groups were treated with cobra venom factor to induce generalized complement depletion and with sublethal irradiation to deplete circulating leukocytes. In C6-depleted rats, C6 levels were reduced to less than 3% of baseline throughout the 2 days of the study compared with over 100% in controls. At 4 h after disease induction, glomerular deposition of antigen and antibody were similar in C6D and control groups by immunofluorescence and by direct measurement of glomerular deposition of radiolabeled antigen and antibody (cationized 131I human IgG, 9.1 +/- 0.1 micrograms/38,000 glomeruli in C6D versus 9.8 +/- 0.9 in controls; P = was not significant; rabbit 125I-labeled anti-human IgG, 104 +/- 10 ng in C6D versus 80 +/- 9 ng in controls; P = was not significant). Circulating C3 levels and glomerular C3 deposition were also similar in C6D and control groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Couser
W G
WG
Department of Medicine, University of Washington, Seattle 98195.
Ochi
R F
RF
Baker
P J
PJ
Schulze
M
M
Campbell
C
C
Johnson
R J
RJ
D000818:Animals; D000941:Antigens; D003183:Complement C6 / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000378:metabolism*; D015938:Complement Membrane Attack Complex / Q000378:metabolism; D007105:Immune Complex Diseases / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D007074:Immunoglobulin G; D007962:Leukocytes / Q000276:immunology; D009393:Nephritis / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D011507:Proteinuria / Q000209:etiology* / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains
D000941:Antigens; D003183:Complement C6; D015938:Complement Membrane Attack Complex; D007074:Immunoglobulin G