Predominant role of FcgammaRIII in the induction of accelerated nephrotoxic glomerulonephritis.
BACKGROUND
Nephrotoxic glomerulonephritis is induced by the administration of antibody against the glomerular basement membrane (GBM). We demonstrated previously that Fc receptors for immunoglobulin G (IgG) (FcgammaR) play crucial roles in the induction of accelerated nephrotoxic glomerulonephritis by using FcRgamma-deficient (-/-) mice. Since FcRgamma-/- mice lack the cell surface expression of two activating FcgammaRs, FcgammaRI and FcgammaRIII. The present study aims to identify the FcgammaR responsible for the induction of nephrotoxic glomerulonephritis.


METHODS
Accelerated anti-GBM glomerulonephritis was induced in FcgammaRI-/-, FcgammaRIII-/-, and FcRgamma-/- mice by preimmunization with rabbit IgG followed by inoculation of rabbit anti-GBM antibody. Histologic analysis and immunostaining of renal sections were performed.


RESULTS
FcgammaRI-/- mice as well as wild-type mice showed severe glomerulonephritis with hypernitremia by the administration of anti-GBM antibody. In contrast, FcgammaRIII-/- mice showed much milder renal involvement, similar to FcRgamma-/- mice. Histologically, FcgammaRI-/- mice showed intracapillary proliferation, glomerular thrombosis, and crescent formation, whereas FcgammaRIII-/- mice showed only glomerular hypercellular changes. The depositions of anti-GBM antibodies, autologous antibodies and complement C3 along the GBM were equally observed among all three FcR-/- mouse types by immunostaining.


CONCLUSIONS
Accelerated nephrotoxic glomerulonephritis is induced predominantly through FcgammaRIII but not FcgammaRI.
Fujii
Takayuki
T
Department of Molecular Genetics, Graduate School of Medicine, Chiba University, Chiba, Japan.
Hamano
Yuki
Y
Ueda
Shiro
S
Akikusa
Bunshiro
B
Yamasaki
Sho
S
Ogawa
Makoto
M
Saisho
Hiromitsu
H
Verbeek
J Sjef
JS
Taki
Shinsuke
S
Saito
Takashi
T
D000419:Albuminuria / Q000209:etiology / Q000652:urine; D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D000906:Antibodies / Q000378:metabolism; D000917:Antibody Formation; D001323:Autoantibodies; D015415:Biomarkers / Q000097:blood; D003176:Complement C3 / Q000378:metabolism; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007678:Kidney Glomerulus / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D011817:Rabbits; D017452:Receptors, IgG / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
D000906:Antibodies; D001323:Autoantibodies; D015415:Biomarkers; D003176:Complement C3; C485701:Fcgr1 protein, mouse; C485700:Fcgr3 protein, mouse; D007074:Immunoglobulin G; D017452:Receptors, IgG; C051951:antiglomerular basement membrane antibody