Eicosanoid production in nonparenchymal liver cells isolated from rats infused with E. coli endotoxin.
Continuous i.v. infusion of a nonlethal dose of Escherichia coli endotoxin induced an early (3-h) accumulation of neutrophils in the rat liver followed by a later (30-h) greater extravasation of mononuclear phagocytes (MNP). These inflammatory cells, recovered together by centrifugal elutriation, were analyzed for their potential capacity to metabolize [1-14C]-AA. Ca2+ ionophore A23187 (5 microM) stimulated the release of [1-14C]-AA from PC and PI both in cells from saline- and ET-infused rats, the latter showing a higher capacity to further metabolize AA to eicosanoids. LTB4 and 5-HETE were the major metabolites accumulated in cells from rats infused with ET for 3 h, while PGD2 played the main role in cells from saline-infused rats. This could reflect [1-14C]-AA metabolism by PMNP and Kupffer cells, respectively. By 30 h of ET-infusion, a shift from PGD2 to PGE2 release was observed. These results suggest that eicosanoids released by nonparenchymal cells (i.e., Kupffer and endothelial cells) and PMNP in the liver of ET-infused rats may alter the normal intercellular information flow between parenchymal and nonparenchymal cells, contributing to the severe impairment in liver function and metabolism during endotoxicosis and sepsis.
Rodriguez de Turco
E B
EB
Department of Physiology, Louisiana State University Medical Center, New Orleans 70112.
Spitzer
J A
JA
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis; D015777:Eicosanoids / Q000096:biosynthesis*; D004731:Endotoxins / Q000633:toxicity*; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis; D007975:Leukotriene B4 / Q000096:biosynthesis; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains
D001095:Arachidonic Acids; D015777:Eicosanoids; D004731:Endotoxins; D006893:Hydroxyeicosatetraenoic Acids; D007975:Leukotriene B4; D016718:Arachidonic Acid; D000001:Calcimycin; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D015232:Dinoprostone