Bowel necrosis induced by tumor necrosis factor in rats is mediated by platelet-activating factor.
We have developed a rat model of ischemic bowel necrosis associated with shock by injection of platelet-activating factor (PAF) or a combination of PAF and endotoxin. Recent investigations have shown that tumor necrosis factor (TNF) also induces shock and necrosis of the gastrointestinal tract. The morphological changes of TNF-induced bowel lesions are indistinguishable from those caused by PAF. The mechanism of TNF-induced bowel necrosis is unclear. In the present study, we have shown that (a) TNF caused PAF production in bowel tissue; (b) the effects of TNF and LPS on PAF production in the intestine are additive; (c) TNF and LPS are synergistic in inducing bowel necrosis; and (d) TNF-induced bowel necrosis is due to PAF release and can be prevented by pretreatment with PAF antagonists.
Sun
X M
XM
Department of Pathology, Children's Memorial Hospital, Northwestern University, Chicago, Illinois 60614.
Hsueh
W
W
D000818:Animals; D004064:Digestive System / Q000098:blood supply / Q000473:pathology*; D004195:Disease Models, Animal; D007511:Ischemia / Q000139:chemically induced* / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D009336:Necrosis; D010972:Platelet Activating Factor / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*
D008070:Lipopolysaccharides; D010972:Platelet Activating Factor; D014409:Tumor Necrosis Factor-alpha