Arachidonic acid metabolites and endothelial injury: studies with cultures of human endothelial cells.
Human endothelial cells in culture can metabolize arachidonic acid to prostaglandin (PG) I2 (prostacyclin), PGE2, and PGF2 alpha, and to various nonpolar products. Similar metabolites are formed by cultured pulmonary arterial and venous cells and umbilical venous cells. In studies with umbilical venous endothelial cells, PG formation was stimulated by mechanical agitation or by treatment with histamine or melittin. Histamine stimulated prostacyclin release into cell culture media without damaging the cells, but melittin injured the cell membrane as indicated by the loss of 51Cr from labeled cells. Media collected from mechanically agitated cells inhibited the release of chromium by melittin. Heating to 56 C or acidification of the media did not reverse this protective effect. Prostacyclin added to labeled cells before challenge with melittin partially inhibited 51Cr release, but PGE2 or leukotrienes B4, C4, and D4 did not. In experiments with pulmonary endothelial cells, histamine augmented the release of hydroxyeicosatetraenoic acids (HETEs) and other nonpolar metabolites. The major nonpolar product comigrated on high-pressure liquid chromatography with di-HETEs. 11-HETE and 15-HETE were identified in media from histamine-stimulated cells by comigration with standards. Neither of these compounds nor 12-HETE protected endothelial cells from melittin-induced injury. It is not yet known if any arachidonic acid metabolites can modulate endothelial cell injury.
Johnson
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Revtyak
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Campbell
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D001095:Arachidonic Acids / Q000378:metabolism*; D002478:Cells, Cultured; D015237:Dinoprost; D015232:Dinoprostone; D004727:Endothelium / Q000378:metabolism* / Q000473:pathology; D011464:Epoprostenol / Q000096:biosynthesis; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis; D007975:Leukotriene B4 / Q000096:biosynthesis; D008555:Melitten / Q000494:pharmacology; D015230:Prostaglandin D2; D011457:Prostaglandins D / Q000096:biosynthesis; D011458:Prostaglandins E / Q000096:biosynthesis; D011460:Prostaglandins F / Q000096:biosynthesis; D011651:Pulmonary Artery / Q000166:cytology; D011667:Pulmonary Veins / Q000166:cytology; D014471:Umbilical Veins / Q000166:cytology
D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D011457:Prostaglandins D; D011458:Prostaglandins E; D011460:Prostaglandins F; D007975:Leukotriene B4; D008555:Melitten; D006632:Histamine; D015237:Dinoprost; D011464:Epoprostenol; D015232:Dinoprostone; D015230:Prostaglandin D2