AJP - Gastrointestinal and Liver Physiology, Vol 263, Issue 6 947-G952, Copyright © 1992 by American Physiological Society
Serum complement mediates endotoxin-induced cysteinyl leukotriene formation in rats in vivo
H. Jaeschke, M. J. Raftery, U. Justesen and S. J. Gaskell
Department of Medicine, Baylor College of Medicine, Houston, Texas 77030.
To investigate potential mediators responsible for cysteinyl leukotriene
formation during endotoxemia, male Fischer rats received an intravenous
bolus injection of 5 mg/kg Salmonella enteritidis endotoxin and cysteinyl
leukotrienes were measured by gas chromatography-mass spectrometry. The
biliary excretion of leukotriene (LT) C4 (0.20 +/- 0.02 pmol.min-1.g
liver-1) and N-acetyl-LTE4 (0.37 +/- 0.07 pmol.min-1.g-1) was increased by
190 and 1,000%, respectively, during the first 30 min after endotoxin
injection. Endotoxin also caused a temporary reduction of hepatic ATP
levels by 84%. Depletion of serum complement almost completely abolished
the endotoxin-induced increase of cysteinyl leukotrienes in bile without
affecting the biliary excretion mechanism. Intravenous injection of
activated complement factors caused cysteinyl leukotriene formation and
reduced the hepatic ATP content similar to endotoxin. Depletion of
glutathione in the liver prevented cysteinyl leukotriene formation and the
complement-induced ATP depletion. It is concluded that endotoxin-induced
cysteinyl leukotriene generation in vivo is mediated predominantly through
activation of complement. The vasoconstrictive cysteinyl leukotrienes are
then responsible for ATP depletion in the liver.
