Superoxide anion generation in the liver during the early stage of endotoxemia in rats.
Infiltration of polymorphonuclear neutrophils (PMN) in the rat liver 3 hr after an intravenous (IV) injection of a sublethal dose of Escherichia coli lipopolysaccharide (LPS) was observed without any significant alteration in the total number of Kupffer and endothelial cells. Since previous studies have demonstrated that phagocytic cells in the liver were in a state of metabolic activation under similar experimental conditions, we investigated the in vitro generation of superoxide anion (O2-) by this cell type following the administration of LPS. Kupffer cells from normal rats did not release O2-, in contrast to those obtained from LPS-treated rats. The generation of O2- by Kupffer cells from endotoxic rats was elevated from 3.0 +/- 1.9 nmol/10(6) cells/60 min (mean +/- SD) in the absence of macrophage (M phi) activators, to 5.0 +/- 2.36, 11.33 +/- 5.40, and 4.33 +/- 0.90 in the presence of opsonized zymosan, phorbol myristate acetate (PMA), and the calcium ionophore A23187, respectively. Hepatocytes from normal or endotoxic rats did not produce detectable O2-. Endothelial cells from LPS-treated rats generated less than 0.8 nmol/10(6) cells in the presence of zymosan. PMN that accumulated in the livers of endotoxic rats released O2- only in the presence of zymosan (8.12 +/- 5.40), PMA (15.43 +/- 5.84), or A23187 (1.70 +/- 0.12). The O2- generation by blood monocytes and PMN increased significantly after endotoxin administration and in the presence of activators. These results suggest that the hypermetabolic state of phagocytic cells in the liver shortly after LPS treatment may be correlated with the increased generation of O2-. The latter may subsequently contribute to the induction of hepatic injury in endotoxemia.
Bautista
A P
AP
Department of Physiology, Louisiana State University Medical Center, New Orleans 70112.
Mészáros
K
K
Bojta
J
J
Spitzer
J J
JJ
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D004731:Endotoxins / Q000097:blood* / Q000633:toxicity; D007728:Kupffer Cells / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000378:metabolism*; D008297:Male; D009000:Monocytes / Q000378:metabolism; D009503:Neutropenia / Q000209:etiology; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004731:Endotoxins; D008070:Lipopolysaccharides; D013481:Superoxides; D000001:Calcimycin; D013755:Tetradecanoylphorbol Acetate