Endotoxin alters arachidonate metabolism in pulmonary endothelial cells.
Endotoxin and lipid A dose dependently (1 ng/ml to 10 micrograms/ml) and time dependently (6-24 h) stimulated the generation of large amounts of prostacyclin in cultured pig pulmonary artery endothelial cells. This effect occurred in the absence of cell detachment and overt cell damage. The presence of at least 1% serum was required but the activation of the complement cascade was not. Endotoxin-treated endothelial cells generated increased amounts of prostacyclin upon stimulation with A23187 and arachidonic acid. Endotoxin-induced activation of arachidonate metabolism could be reduced by 10(-10) M glucocorticoids but not by progesterone. It was further affected by inhibitors of protein and RNA synthesis and calmodulin function. In addition, exposure of endothelial cells to endotoxin resulted in an enhanced synthesis of cyclooxygenase and in a higher enzymatic capacity of prostacyclin synthase. The data indicate that endotoxin in concentrations occurring in the plasma of patients profoundly alters arachidonic acid metabolism in endothelial cells.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D004727:Endothelium / Q000166:cytology / Q000378:metabolism; D004731:Endotoxins / Q000494:pharmacology*; D011464:Epoprostenol / Q000378:metabolism; D008050:Lipid A / Q000494:pharmacology; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D012475:Salmonella; D013552:Swine
D001095:Arachidonic Acids; D004731:Endotoxins; D008050:Lipid A; D016718:Arachidonic Acid; D011464:Epoprostenol