Lipopolysaccharide-induced glomerulonephritis develops in the absence of interferon-gamma signaling

Exp Nephrol. 1996 Jul-Aug;4(4):222-30.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Antinuclear / blood
  • Antibodies, Monoclonal
  • Escherichia coli
  • Female
  • Glomerulonephritis / chemically induced
  • Glomerulonephritis / immunology*
  • Glomerulonephritis / pathology*
  • Histocompatibility Antigens Class I / analysis
  • Histocompatibility Antigens Class II / analysis
  • Homozygote
  • Immunoglobulin G / blood
  • Intercellular Adhesion Molecule-1 / analysis
  • Intercellular Adhesion Molecule-1 / biosynthesis
  • Interferon-gamma / deficiency*
  • Interferon-gamma / physiology
  • Kidney Cortex / immunology*
  • Kidney Cortex / pathology
  • Lipopolysaccharides
  • Mice
  • Mice, Inbred Strains
  • Mice, Knockout
  • Signal Transduction

Substances

  • Antibodies, Antinuclear
  • Antibodies, Monoclonal
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Immunoglobulin G
  • Lipopolysaccharides
  • Intercellular Adhesion Molecule-1
  • Interferon-gamma