Release of eicosanoids from white blood cells, platelets, smooth muscle cells, and endothelial cells in response to endotoxin and A23187.
Endotoxin produces numerous pathophysiologic changes in animals, including vascular endothelial cell damage and hematologic changes. Direct effects of endotoxin on arachidonic acid metabolism and the release of eicosanoids from endothelial cells and neutrophils have been reported. A rapid release of these autocoids occurs when cells are incubated with endotoxin, and this appears to be one of the earliest endotoxin-induced changes. Some of these eicosanoids may result in beneficial effects, and others may result in detrimental effects. This study was to determine the release of eicosanoids from white blood cells, platelets, smooth muscle cells, and endothelial cells in response to varying amounts of endotoxin and the calcium ionophore A23187. The results indicate that endotoxin has a major direct effect on vascular endothelial cells and smooth muscle cells as indicated by its ability to increase the synthesis of predominately i6-keto-PGF1 alpha by these cells. These effects were seen within a dose range of endotoxin that is lethal in horses. Very high concentrations of endotoxin (100 micrograms/ml) were required to stimulate a small increase in the production of i6-keto-PGF1 alpha and iLTC4 by freshly isolated neutrophils. Stimulation of cells with A23187 revealed that, of the eicosanoids measured, the one produced predominately by endothelial cells and smooth muscle cells was 6-keto-PGF1 alpha, by platelets was TxB2, and by neutrophils was LTC4 (LTB4 was not measured). A mixture of all white blood cells including platelets when incubated with A23187 produced large amounts of TxB2, LTB4, and LTC4 with smaller amounts of 6-keto-PGF1 alpha. The results indicate that endotoxin directly affects cells and stimulates them to produce thromboxane and prostacyclin, but very high concentrations of endotoxin were required to stimulate neutrophils to produce rather small increases in iLTC4.
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology*; D002478:Cells, Cultured; D004727:Endothelium / Q000378:metabolism; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D006736:Horses; D007962:Leukocytes / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis*; D011863:Radioimmunoassay; D013189:SRS-A / Q000096:biosynthesis; D013929:Thromboxane B2 / Q000096:biosynthesis
D004731:Endotoxins; D011453:Prostaglandins; D013189:SRS-A; D000001:Calcimycin; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha