Prevention of crescentic glomerulonephritis induced by anti-glomerular membrane antibody in tumor necrosis factor-deficient mice.
Tumor necrosis factor (TNF) is a proinflammatory cytokine playing a central role in the expression of endothelial adhesion molecules required for the recruitment of inflammatory cells. Proliferative glomerulonephritis induced by anti-glomerular basement membrane (GBM) antibody is characterized by the recruitment of inflammatory cells in the glomerulus followed by capillary damage and crescent formation. The glomerular pathology may be due to a large extent to TNF induction. We therefore tested this hypothesis in TNF-deficient mice. Anti-GBM antibody administration in sensitized wild-type mice resulted in deposition of immune complexes, followed by increased intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression, as well as the influx of polymorphonuclear neutrophils (PMNs), lymphocytes, and macrophages. Distinct proteinuria preceded proliferative glomerulonephritis characterized by crescent formation. In the absence of TNF, the development of proteinuria was delayed and the formation of crescents was almost completely prevented. Although the deposition of immune complexes in glomeruli was comparable in both groups, the up-regulation of ICAM-1 and VCAM-1, as well as the influx of PMNs and lymphocytes, but not of monocytes, was dramatically reduced in TNF-deficient mice. Therefore, we conclude that TNF plays a key role in the recruitment of inflammatory cells and in the subsequent development of proliferative glomerulonephritis.
Le Hir
M
M
Institute of Anatomy, University of Zurich, Switzerland.
Haas
C
C
Marino
M
M
Ryffel
B
B
D000818:Animals; D000917:Antibody Formation; D001485:Basement Membrane / Q000276:immunology; D003433:Crosses, Genetic; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D005921:Glomerulonephritis / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D007111:Immunity, Cellular; D007074:Immunoglobulin G; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000235:genetics; D007668:Kidney / Q000276:immunology* / Q000473:pathology; D007678:Kidney Glomerulus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D011507:Proteinuria; D011817:Rabbits; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis / Q000235:genetics
D007074:Immunoglobulin G; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1