Lipopolysaccharide-induced glomerulonephritis develops in the absence of interferon-gamma signaling.
IFN gamma is a costimulator of macrophage activation and it plays an important role as a proinflammatory cytokine by upregulation of adhesion molecules and MHC antigens. In this study we tested the role of IFN gamma in a model of endotoxin-induced glomerulonephritis. A systemic lupus-like disease was induced by injection of 50 micrograms bacterial LPS twice a week for 4 weeks in wild-type and in IFN gamma receptor-deficient (IFN gamma R-/-) mice. The renal cortex was examined by immunofluorescence and by light microscopy. LPS treatment induced an increase in serum levels of IgG and anti-dsDNA antibodies. A mild glomerulonephritis was characterized morphologically, but proteinuria was not observed. The main histological features of glomerulonephritis were an increase in ICAM-1 expression, deposition of immune complexes and of complement in the glomeruli, increased mesangial matrix and mesangial hypercellularity. The number of intraglomerular leukocytes, detected by MHC class-II and LFA-1 expression increased roughly 4-fold. All those alterations took place in a similar manner in wild-type and in IFN gamma R-/-mice. Therefore it is concluded that IFN gamma does not play an important role in the development of endotoxic glomerulonephritis.
Haas
C
C
Institute of Toxicology, University of Zürich, Switzerland.
Car
B
B
Ryffel
B
B
Le Hir
M
M
D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D000911:Antibodies, Monoclonal; D004926:Escherichia coli; D005260:Female; D005921:Glomerulonephritis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology*; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006720:Homozygote; D007074:Immunoglobulin G / Q000097:blood; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000096:biosynthesis; D007371:Interferon-gamma / Q000172:deficiency* / Q000502:physiology; D007672:Kidney Cortex / Q000276:immunology* / Q000473:pathology; D008070:Lipopolysaccharides; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D015398:Signal Transduction
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma