Immunohistochemical characterization of glomerular inflammatory cells and expression of adhesion molecules in anti-glomerular basement membrane (anti-GBM) glomerulonephritis induced in WKY rats with monoclonal anti-GBM antibodies of different subclasses.
According to previous report, adhesion of CD8-positive cells and macrophages to glomerular endotherial cells through the lymphocyte function-associated antigen-1 (LFA-1)/intercellular adhesion molecule-1 (ICAM-1) pathway is crucial for the initiation and subsequent progression of anti-glomerular basement membrane (anti-GBM) antibody-induced glomerulonephritis (anti-GBM nephritis) in WKY rats. In the present study glomerular inflammatory cell infiltration and LFA-1/ICAM-1 expression were examined in anti-GBM nephritis induced in WKY rats with monoclonal anti-GBM antibodies of different subclasses: IgG1, IgG2a, and IgG2b. The IgG2a and IgG2b subclasses induced significant proteinuria from day 3 as compared with the IgG1 subclass. Glomerular infiltration of macrophages and CD8-positive cells after administration of IgG2a and IgG2b subclass antibodies was significantly elevated compared to that for the IgG1 subclass. The intensity of glomerular ICAM-1 immunostaining by the IgG2a and IgG2b subclass antibodies tended to be stronger than that by the IgG1 subclass. Glomerular LFA-1-positive cell infiltration by the IgG2a and IgG2b subclasses was significantly higher than that of the IgG1 subclass. These results demonstrate that monoclonal antibodies belonging to the IgG2a and IgG2b subclasses strongly induce glomerular infiltration of inflammatory cells and expression of adhesion molecules in rat anti-GBM nephritis.
Kado
Tadashi
T
Division of Pediatrics and Perinatology, Faculty of Medicine, Tottori University, Yonago, Japan. CYY03617@nifty.ne.jp
Kohda
Takayuki
T
Okada
Shinichi
S
Hayashi
Atsushi
A
Utsunomiya
Yasushi
Y
Kanzaki
Susumu
S
Sado
Yoshikazu
Y
Yamamoto
Tadashi
T
D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D000906:Antibodies / Q000276:immunology; D001323:Autoantibodies; D049109:Cell Proliferation; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis* / Q000235:genetics; D007678:Kidney Glomerulus / Q000737:chemistry* / Q000473:pathology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis* / Q000235:genetics; D008264:Macrophages / Q000473:pathology; D051381:Rats; D011921:Rats, Inbred WKY
D000906:Antibodies; D001323:Autoantibodies; D007074:Immunoglobulin G; D016169:Lymphocyte Function-Associated Antigen-1; C051951:antiglomerular basement membrane antibody; D018799:Intercellular Adhesion Molecule-1