TY - JOUR
T1 - Predominant role of FcγRIII in the induction of accelerated nephrotoxic glomerulonephritis
AU - Fujii, Takayuki
AU - Hamano, Yuki
AU - Ueda, Shiro
AU - Akikusa, Bunshiro
AU - Yamasaki, Sho
AU - Ogawa, Makoto
AU - Saisho, Hiromitsu
AU - Verbeek, J. Sjef
AU - Taki, Shinsuke
AU - Saito, Takashi
N1 - Funding Information:
We thank Dr. K. Takase for discussion, Dr. S.-M. Chen for antibody preparation, Ms. M. Sakuma and Ms R. Shiina for technical assistance, and Ms. H. Yamaguchi and Ms Y. Kurihara for secretarial assistance. This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Science and Culture, and the Ministry of Health, Labor and Welfare Japan.
PY - 2003/10/1
Y1 - 2003/10/1
N2 - 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) (FcγR) play crucial roles in the induction of accelerated nephrotoxic glomerulonephritis by using FcRγ-deficient (-/-) mice. Since FcRγ-/- mice lack the cell surface expression of two activating FcγRs, FcγRI and FcγRIII. The present study aims to identify the FcγR responsible for the induction of nephrotoxic glomerulonephritis. Methods. Accelerated anti-GBM glomerulonephritis was induced in FcγRI-/-, FcγRIII-/-, and FcRγ-/- mice by preimmunization with rabbit IgG followed by inoculation of rabbit anti-GBM antibody. Histologic analysis and immunostaining of renal sections were performed. Results. FcγRI-/- mice as well as wild-type mice showed severe glomerulonephritis with hypernitremia by the administration of anti-GBM antibody. In contrast, FcγRIII-/- mice showed much milder renal involvement, similar to FcRγ-/-mice. Histologically, FcγRI-/- mice showed intracapillary proliferation, glomerular thrombosis, and crescent formation, whereas FcγRIII-/- 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 FcγRIII but not FcγRI.
AB - 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) (FcγR) play crucial roles in the induction of accelerated nephrotoxic glomerulonephritis by using FcRγ-deficient (-/-) mice. Since FcRγ-/- mice lack the cell surface expression of two activating FcγRs, FcγRI and FcγRIII. The present study aims to identify the FcγR responsible for the induction of nephrotoxic glomerulonephritis. Methods. Accelerated anti-GBM glomerulonephritis was induced in FcγRI-/-, FcγRIII-/-, and FcRγ-/- mice by preimmunization with rabbit IgG followed by inoculation of rabbit anti-GBM antibody. Histologic analysis and immunostaining of renal sections were performed. Results. FcγRI-/- mice as well as wild-type mice showed severe glomerulonephritis with hypernitremia by the administration of anti-GBM antibody. In contrast, FcγRIII-/- mice showed much milder renal involvement, similar to FcRγ-/-mice. Histologically, FcγRI-/- mice showed intracapillary proliferation, glomerular thrombosis, and crescent formation, whereas FcγRIII-/- 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 FcγRIII but not FcγRI.
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U2 - 10.1046/j.1523-1755.2003.00203.x
DO - 10.1046/j.1523-1755.2003.00203.x
M3 - Article
C2 - 12969160
AN - SCOPUS:0141563508
VL - 64
SP - 1406
EP - 1416
JO - Kidney International
JF - Kidney International
SN - 0085-2538
IS - 4
ER -