title: Adipose triglyceride lipase regulates eicosanoid production in activated human mast cells.
abstract: Human mast cells (MCs) contain TG-rich cytoplasmic lipid droplets (LDs) with high arachidonic acid (AA) content. Here, we investigated the functional role of adipose TG lipase (ATGL) in TG hydrolysis and the ensuing release of AA as substrate for eicosanoid generation by activated human primary MCs in culture. Silencing of ATGL in MCs by siRNAs induced the accumulation of neutral lipids in LDs. IgE-dependent activation of MCs triggered the secretion of the two major eicosanoids, prostaglandin D2 (PGD2) and leukotriene C4 (LTC4). The immediate release of PGD2 from the activated MCs was solely dependent on cyclooxygenase (COX) 1, while during the delayed phase of lipid mediator production, the inducible COX-2 also contributed to its release. Importantly, when ATGL-silenced MCs were activated, the secretion of both PGD2 and LTC4 was significantly reduced. Interestingly, the inhibitory effect on the release of LTC4 was even more pronounced in ATGL-silenced MCs than in cytosolic phospholipase A2-silenced MCs. These data show that ATGL hydrolyzes AA-containing TGs present in human MC LDs and define ATGL as a novel regulator of the substrate availability of AA for eicosanoid generation upon MC activation.
authors.affiliation: Wihuri Research Institute, 00290 Helsinki, Finland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Dichlberger
authors.affiliation: Wihuri Research Institute, 00290 Helsinki, Finland.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Schlager
authors.affiliation: Wihuri Research Institute, 00290 Helsinki, Finland.
authors.forename: Katariina
authors.initials: K
authors.lastname: Maaninka
authors.affiliation: Department of Medical Biochemistry, Medical University Vienna, Max F. Perutz Laboratories, 1030 Vienna, Austria.
authors.forename: Wolfgang J
authors.initials: WJ
authors.lastname: Schneider
authors.affiliation: Wihuri Research Institute, 00290 Helsinki, Finland.
authors.forename: Petri T
authors.initials: PT
authors.lastname: Kovanen
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism*; D002478:Cells, Cultured; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015777:Eicosanoids / Q000378:metabolism*; D020868:Gene Silencing; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism; D007700:Kinetics; D017997:Leukotriene C4 / Q000378:metabolism; D008049:Lipase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D066292:Lipid Droplets / Q000378:metabolism*; D008066:Lipolysis; D008407:Mast Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D054510:Phospholipases A2, Cytosolic / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015230:Prostaglandin D2 / Q000378:metabolism; D034741:RNA, Small Interfering; D014280:Triglycerides / Q000378:metabolism*; D000217:Acyltransferases
chemical_list: D018952:Antigens, CD34; D016718:Arachidonic Acid; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015777:Eicosanoids; D007073:Immunoglobulin E; D017997:Leukotriene C4; D008049:Lipase; D054510:Phospholipases A2, Cytosolic; D015230:Prostaglandin D2; D034741:RNA, Small Interfering; D014280:Triglycerides; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; C494794:PNPLA2 protein, human; D000217:Acyltransferases
keywords: arachidonic acid; leukotrienes; lipid droplets; lipolysis and fatty acid metabolism; phospholipases/A2; prostaglandins
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