Prostaglandin E2 limits arachidonic acid availability and inhibits leukotriene B4 synthesis in rat alveolar macrophages by a nonphospholipase A2 mechanism
Christman, B.W.; Christman, J.W.; Dworski, R.; Blair, I.A.; Prakash, C.
Journal of Immunology 151(4): 2096-2104
1993
ISSN/ISBN: 0022-1767 PMID: 8393898 Document Number: 405510
Prostaglandin E-2 (PGE-2), a potent mediator of inflammation released in large amounts by endotoxin-stimulated alveolar macrophages (AM), has been shown to inhibit leukotriene B-4 (LTB-4) release by activated neutrophils. We investigated the hypothesis that LTB-4 synthesis by AM can be regulated by PGE-2 and performed experiments to determine the biochemical site of regulation. AM obtained from Sprague-Dawley rats were preincubated with PGE-2 before stimulation with the calcium ionophore A23187. LTB-4, platelet-activating factor (PAF), lysoPAF, (AA), and 5-hydroxyeicosatetraenoic acid were isolated from AM cells and supernatants, then quantified by gas chromatography/electron capture negative ion mass spectrometry. Stimulated AM released 30.50 +- 4.52 ng LTB-4/10-6 cells and were inhibited by PGE-2 in a dose dependent manner. PGE-2 (1 mu-M) inhibited LTB-4 synthesis by 37% and decreased release of both 5-hydroxyeicosatetraenoic acid and arachidonic acid by stimulated AM, but did not alter synthesis of PAF or lysoPAF. These mass measurements suggest that PGE-2 does not affect the activity of phospholipase A2, PAF acetyltransferase, leukotriene A-4 hydrolase. We conclude that PGE-2 attenuates LTB-4 production in alveolar macrophages by altering the activity of lipases other than phospholipase A-2. PGE-2-mediated inhibition of LTB-4 synthesis by AM may regulate the initiation of lung inflammation.