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J Am Soc Nephrol 14: 1785–1793, 2003 Intrinsic Renal Cells Are the Major Source of Tumor Necrosis Factor Contributing to Renal Injury in Murine Crescentic

By Jennifer R. Timoshanko, Jonathon D. Sedgwick, Stephen R. Holdsworth and Peter G. Tipping


Abstract. Macrophages are prominent participants in crescentic glomerulonephritis (GN) and have been suggested to be the major source of TNF in this cell-mediated form of glomerular inflammation. Intrinsic renal cells also have the capacity to produce TNF. For dissecting the contribution of local versus bone marrow (BM)–derived TNF in inflammatory renal injury, TNF chimeric mice were created by transplanting normal wildtype (WT) BM into irradiated TNF-deficient recipients (WT3TNF �/ � chimeras) and vice versa (TNF �/ � 3WT chimeras). A model of crescentic GN induced by an intravenous injection of sheep anti-murine glomerular basement membrane antibody was studied in WT mice, mice with complete TNF deficiency (TNF�/�), and chimeric mice. Crescentic GN was attenuated in TNF�/ � mice with fewer crescents (crescents, 13.7 � 1.7 % of glomeruli) and reduced functional indices o

Year: 2013
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