Hepatic neutrophil influx: eicosanoid and superoxide formation in endotoxemia.
We examined early changes, at 0.5, 1.5, and 3 hr of infusion of a nonlethal dose of Escherichia coli endotoxin (ET) in neutrophil (PMN) sequestration in the liver and accompanying alterations in [1-14C]arachidonic acid metabolism and superoxide anion release by Kupffer and endothelial cells and PMNs. One hundred fifty micrograms ET (268 micrograms/kg) was infused over 3 hr. Shorter infusions delivered proportionally less ET. By 30 min of ET infusion the number of PMNs in the 45 ml/min fraction was 2.41 x 10(7), eightfold higher than that in the NaCl-infused rats, representing 35.90 +/- 3.49% (n = 7) of the total cell yield vs 8.20 +/- 0.20% (n = 4) in NaCl controls. By 90 and 180 min of ET infusion the number of PMNs and their share of the total cell yield increased significantly further. Cells were separated by elutriation, followed by application of a Ficoll-Hypaque gradient, when appropriate. Kupffer cells and PMNs were recovered in the 45 ml/min fraction, endothelial cells in the 23 ml/min fraction. At 30 min of ET infusion the profile of arachidonic acid metabolites released from [1-14C]arachidonic acid-prelabeled nonparenchymal cells upon A23187 stimulation was not different from that of cells of NaCl-infused rats. Infusion of ET for 90 min accentuated PMN infiltration, and resulted in significant modulation of the eicosanoid profile, consisting of a major shift in PGD2/PGE2 to PGE2, and LTB4 and 12-HETE accounting for 34% of the total eicosanoids, compared to 12.9% in time-matched NaCL controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Spitzer
J A
JA
Department of Physiology, Louisiana State University Medical Center, New Orleans 70112-1393.
Mayer
A M
AM
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte; D015232:Dinoprostone / Q000378:metabolism; D015777:Eicosanoids / Q000096:biosynthesis*; D004731:Endotoxins / Q000008:administration & dosage / Q000097:blood*; D004926:Escherichia coli; D007700:Kinetics; D007728:Kupffer Cells / Q000166:cytology; D007975:Leukotriene B4 / Q000378:metabolism; D008099:Liver / Q000166:cytology*; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D010101:Oxygen Consumption; D015230:Prostaglandin D2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism*
D015777:Eicosanoids; D004731:Endotoxins; D013481:Superoxides; D007975:Leukotriene B4; D016718:Arachidonic Acid; D000001:Calcimycin; D015232:Dinoprostone; D015230:Prostaglandin D2