Failure to induce anti-glomerular basement membrane glomerulonephritis in TNF alpha/beta deficient mice.
TNF is a key 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-GBM antibody is characterized by the recruitment of inflammatory cells into the glomerulus and capillary damage followed by regeneration with crescent formation. The glomerular pathology may be due to TNF induction and we therefore tested this hypothesis in TNF alpha/beta deficient mice. Anti-GBM antibody administration in sensitised wild-type mice resulted in deposition of immune complexes and complement factor 3, followed by increased ICAM-1 and VCAM-1 expression and influx of polymorphonuclear leucocytes. Distinct proteinuria precedes proliferative glomerulonephritis with glomerular crescent formation, which is fully developed at 10 days. By contrast, no glomerulonephritis developed in TNF alpha/beta deficient mice. Comparable antibody complex deposits are found, but the upregulation of ICAM-1 and VCAM-1, the influx of inflammatory cells and the subsequent tissue damage is absent in TNF alpha/beta deficient mice. Therefore, we conclude that TNF plays a key role for the recruitment of inflammatory cells by preventing the upregulation of endothelial adhesion molecule and the subsequent development of proliferative glomerulonephritis.
D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism; D001485:Basement Membrane / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005921:Glomerulonephritis / Q000276:immunology* / Q000473:pathology; D007105:Immune Complex Diseases / Q000276:immunology* / Q000473:pathology; D007678:Kidney Glomerulus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D011507:Proteinuria / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000276:immunology*; D015854:Up-Regulation