Mechanisms of glomerular injury in experimental immune nephritis. I. Tumor necrosis factor is released by renal glomeruli of nephritic rats.
Cytotoxic activity expressed by renal glomeruli of LEW rats with the accelerated autologous form of nephrotoxic serum nephritis (AA-NTSN) was assessed using the lymphotoxin (LT) sensitive line aL929. Glomeruli isolated on day 3 following nephritis induction were much more cytotoxic for aL929 in coculture than glomeruli of unmodified LEW (p less than 0.0025). Such a cytolysis was due to a soluble factor eluted on gel chromatography in a single peak corresponding to molecular weight (MW) of 40-45 kDa. The cytotoxic activity, harvested in 24-hour culture supernatants of nephritic glomeruli (NGS) and the chromatographic peak were totally inhibitable by antiserum neutralizing recombinant murine tumor necrosis factor alpha (rMuTNF). An abundant glomerular macrophage accumulation on day 3 and reduction of cytotoxicity (42.3%, p less than 0.01) upon irradiation limiting the mononuclear phagocyte infiltrate suggest that macrophages are at least partly responsible for TNF production by nephritic glomeruli. This study provides the initial documentation on generation of TNF in glomerular inflammatory injury induced by immune reaction.
Hruby
Z W
ZW
Department of Nephrology, Academy of Medicine, Wrocław, Poland.
Lowry
R P
RP
D000419:Albuminuria / Q000209:etiology; D000818:Animals; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D007678:Kidney Glomerulus / Q000276:immunology / Q000293:injuries* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D008297:Male; D009393:Nephritis / Q000209:etiology* / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D014409:Tumor Necrosis Factor-alpha