Abolition of anti-glomerular basement membrane antibody-mediated glomerulonephritis in FcRgamma-deficient mice.
Several recent studies have demonstrated the central role of Fc receptors (FcR) rather than the complement system in triggering hypersensitivity reactions. We investigated the role of FcR for IgG (FcgammaR) using a murine model of accelerated anti-glomerular basement membrane (GBM) antibody-mediated glomerulonephritis as a representative of type II hypersensitivity diseases. Intravenous injection of rabbit anti-GBM antibody after preimmunization with normal rabbit IgG induced proteinuria and azotemia in wild-type C57BL/6 and CD40(+/-) mice but not in FcR gamma chain (FcRgamma)(-/-) mice or CD40(-/-) mice. Light microscopic findings revealed marked tissue damage in the glomeruli of wild-type C57BL/6 and CD40(+/-) mice. However, no tissue damage except polymorphonuclear cell infiltration was observed in the glomeruli of FcRgamma(-/-) mice. The glomeruli of CD40(-/-) mice were almost normal. Immunohistochemistry revealed the binding of rabbit IgG to the GBM in all mice injected with anti-GBM antibody. However, depositions of mouse IgG and complement to the glomeruli were not observed in CD40(-/-) mice, and deposition of fibrin was not observed in FcRgamma(-/-) or CD40(-/-) mice. These findings suggest that FcgammaR may initiate anti-GBM antibody-mediated renal disease. We conclude that FcgammaR rather than the complement system is critically involved in the development of type II hypersensitivity diseases.
Wakayama
H
H
First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan.
Hasegawa
Y
Y
Kawabe
T
T
Hara
T
T
Matsuo
S
S
Mizuno
M
M
Takai
T
T
Kikutani
H
H
Shimokata
K
K
D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000936:Antigen-Antibody Complex / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D001485:Basement Membrane / Q000276:immunology / Q000473:pathology; D019013:CD40 Antigens / Q000235:genetics / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology; D005260:Female; D005337:Fibrin / Q000378:metabolism; D017353:Gene Deletion; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology; D007958:Leukocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000276:immunology; D011507:Proteinuria / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011817:Rabbits; D017452:Receptors, IgG / Q000172:deficiency* / Q000235:genetics / Q000276:immunology*; D014511:Uremia / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D019013:CD40 Antigens; D007074:Immunoglobulin G; D017452:Receptors, IgG; D005337:Fibrin; D003165:Complement System Proteins