Endotoxin-induced eicosanoid production by equine vascular endothelial cells and neutrophils.
Dispersed equine vascular endothelial cells grown in tissue culture, and freshly isolated neutrophils were used to determine direct effects of endotoxin on cyclooxygenase and lipoxygenase products. Endothelial cells (10(7)/ml) or neutrophils (2 X 10(6)/ml) were incubated with (a) buffer, (b) endotoxin (10 micrograms/ml), (c) endotoxin + flunixin meglumine (10 micrograms/ml), or (d) calcium ionophore, A23187 (10 micrograms/ml). Thromboxane (TxB2), prostacyclin (6-keto-PGF1 alpha), and leukotriene C4 (LTC4) were determined in the incubation fluid by radioimmunoassay. Thromboxane and prostacyclin levels increased in endothelial cells incubated with endotoxin. Treatment with flunixin meglumine prevented the endotoxin-induced release of these cyclooxygenase products to levels below those observed in control cells. Leukotriene production was increased in endothelial cells incubated with endotoxin plus flunixin meglumine. Endotoxin as well as endotoxin plus flunixin meglumine increased the production of prostacyclin and LTC4 by freshly isolated neutrophils. Cells exposed to endotoxin plus flunixin meglumine produced more LTC4 than cells exposed to endotoxin. The data revealed that endotoxin has a direct effect on arachidonic acid metabolism in endothelial cells and neutrophils. Flunixin meglumine reduced the level of cyclooxygenase products but increased the level of lipoxygenase products. Therefore, the well-established beneficial effects of cyclooxygenase inhibitors during endotoxemia may be improved even more if they are used in conjunction with lipoxygenase inhibitors or a combined cyclooxygenase-lipoxygenase inhibitor.
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003002:Clonixin / Q000031:analogs & derivatives / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors; D004727:Endothelium / Q000166:cytology / Q000378:metabolism; D004731:Endotoxins / Q000633:toxicity*; D004926:Escherichia coli; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D006736:Horses; D009504:Neutrophils / Q000378:metabolism; D011651:Pulmonary Artery / Q000166:cytology; D011667:Pulmonary Veins / Q000166:cytology; D013189:SRS-A / Q000378:metabolism; D013929:Thromboxane B2 / Q000378:metabolism
D016861:Cyclooxygenase Inhibitors; D004731:Endotoxins; D005231:Fatty Acids, Unsaturated; D013189:SRS-A; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C014558:flunixin meglumine; D003002:Clonixin