| Abstract: |
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. |
| Keywords: |
protein expression; histopathology; pathogenesis; nonhuman; animal cell; mouse; animals; mice; mice, knockout; animal tissue; basement membrane; vascular cell adhesion molecule 1; animal experiment; animal model; mice, inbred c57bl; inflammatory cell; mice, inbred strains; gene expression regulation; kidney; tumor necrosis factor-alpha; immunoglobulin g; blood vessel injury; cell migration; glomerulonephritis; proteinuria; intercellular adhesion molecule 1; antibody formation; tumor necrosis factor; intercellular adhesion molecule-1; immunity, cellular; rabbits; crosses, genetic; vascular cell adhesion molecule-1; immune complex deposition; kidney glomerulus; female; priority journal; article; glomerulus basement membrane antibody
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