title: Predominant role of FcgammaRIII in the induction of accelerated nephrotoxic glomerulonephritis.
abstract: 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.
authors.affiliation: Department of Molecular Genetics, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Fujii
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hamano
authors.forename: Shiro
authors.initials: S
authors.lastname: Ueda
authors.forename: Bunshiro
authors.initials: B
authors.lastname: Akikusa
authors.forename: Sho
authors.initials: S
authors.lastname: Yamasaki
authors.forename: Makoto
authors.initials: M
authors.lastname: Ogawa
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Saisho
authors.forename: J Sjef
authors.initials: JS
authors.lastname: Verbeek
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Taki
authors.forename: Takashi
authors.initials: T
authors.lastname: Saito
mesh_terms: 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
chemical_list: 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