Cell-to-cell interaction is required to induce proteinuria in in situ immune complex glomerulonephritis.
This experiment was performed to study the roles of intercellular adhesion molecule-1 (ICAM-1), lymphocyte function-associated antigen-1 (LFA-1), and another adhesion molecule, selectin, in the development of cationized antigen-induced in situ immune complex glomerulonephritis (CAICGN). CAICGN was induced in preimmunized rats by perfusing cationized human immunoglobulin G (CaIgG) through the left kidney. Albuminuria developed within 2 days of CaIgG perfusion and peaked around day 7. Marked polymorphonuclear leukocyte (PMN) infiltration was observed in the glomeruli 1 hour after CaIgG perfusion, but the infiltrate resolved by day 7. Immunofluorescent studies disclosed linear deposition of rat IgG and C3 along glomerular capillary walls 1 hour after CaIgG perfusion. Treatment with monoclonal antibodies (mAbs) to both ICAM-1 and LFA-1, as well as with a sulfatide, a ligand of L- and P-selectin, started within 2 days after CaIgG perfusion completely suppressed the development of proteinuria without affecting the glomerular deposition of immunoreactants. Although sulfatide attenuated the PMN response 1 hour after CaIgG perfusion, ICAM-1 and LFA-1 mAb treatment did not alter PMN infiltration. Treatment with ICAM-1 and LFA-1 mAbs started on day 5, or treatment with sulfatide started on day 4, after CaIgG perfusion did not affect albuminuria. These findings suggest that adhesion molecules play an important role in the development of proteinuria in CAICGN. The contribution of these molecules was evident for only a short interval after the induction of nephritis, when a significant infiltration of PMNs was observed.
Department of Internal Medicine, Hamamatsu University School of Medicine, Japan.
T
T
Oda
M
M
Kimura
A
A
Hishida
A
A
Yamashita
Y
Y
Suzuki
M
M
Miyasaka
D000419:Albuminuria / Q000276:immunology; D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology*; D002412:Cations; D002450:Cell Communication; D005455:Fluorescent Antibody Technique; D005921:Glomerulonephritis / Q000276:immunology* / Q000473:pathology* / Q000652:urine; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis / Q000276:immunology; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D008297:Male; D009504:Neutrophils / Q000473:pathology; D011507:Proteinuria / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019087:Selectins / Q000276:immunology
D000936:Antigen-Antibody Complex; D002412:Cations; D007074:Immunoglobulin G; D016169:Lymphocyte Function-Associated Antigen-1; D019087:Selectins; D018799:Intercellular Adhesion Molecule-1