title: Evidence for Kupffer cell activation by burn injury and Pseudomonas exotoxin A.
abstract: Postburn metabolic and immunological alterations may in part be due to translocation of gut exotoxin and endotoxin, which can result in tumour necrosis factor (TNF) and prostaglandin E (PGE) production by macrophages. We evaluated the effect of burn injury, plus exotoxin and endotoxin on TNF-alpha and PGE production by Kupffer cells, and peritoneal macrophages. Adult Wistar rats underwent 30 per cent TBSA burn or sham burn. Kupffer cells were harvested from rat livers and peritoneal macrophages from the abdominal cavity 24 h postburn. They were cultured overnight at 1 x 10(6) cells/ml and stimulated with saline, 5 micrograms/ml of Pseud. aeruginosa Exotoxin A (Exo-A), 5 micrograms/ml of Pseud. aeruginosa Endotoxin (Endo), Exo-A + Endo, or Exo-A + Endo + the PGE derivative 16,16 dimethyl-PGE (dPGE) (10 micrograms/ml). The supernatants were harvested after 4, 24 and 48 h of culture and assayed for TNF-alpha and PGE. Results showed that burn injury induced an increase in TNF-alpha and PGE production by Kupffer cells stimulated with Exo-A, Endo, and both Exo-A + Endo (P < 0.05). The release of TNF-alpha by Kupffer cells was downregulated by exogenous PGE (P < 0.05). The increased TNF-alpha production was inversely related to PGE levels. In conclusion, both burn injury and Exo-A potentiate the responsiveness of Kupffer cells and peritoneal macrophages to endotoxin as measured by the rate of production of TNF-alpha and PGE. PGE may locally downregulate the immune response by limiting Kupffer cells' and peritoneal macrophages' TNF-alpha production.
authors.affiliation: Shriners Burns Institute, Galveston Unit, Texas.
authors.forename: Y L
authors.initials: YL
authors.lastname: Dong
authors.forename: F
authors.initials: F
authors.lastname: Ko
authors.forename: T
authors.initials: T
authors.lastname: Yan
authors.forename: H Q
authors.initials: HQ
authors.lastname: Huang
authors.forename: D N
authors.initials: DN
authors.lastname: Herndon
authors.forename: J P
authors.initials: JP
authors.lastname: Waymack
mesh_terms: D036002:ADP Ribose Transferases; D000818:Animals; D001427:Bacterial Toxins; D002056:Burns / Q000276:immunology*; D002478:Cells, Cultured; D005098:Exotoxins / Q000502:physiology*; D007111:Immunity, Cellular; D007728:Kupffer Cells / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D008297:Male; D011458:Prostaglandins E / Q000096:biosynthesis; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
chemical_list: D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D005098:Exotoxins; D011458:Prostaglandins E; D014409:Tumor Necrosis Factor-alpha; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A