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Activated platelets and monocytes generate four hydroxyphosphatidylethanolamines via lipoxygenase

Maskrey, BH; Bermudez-Fajardo, A; Morgan, AH; Stewart-Jones, E; Dioszeghy, V; Taylor, GW; Baker, PRS; ... O'Donnell, VB; + view all (2007) Activated platelets and monocytes generate four hydroxyphosphatidylethanolamines via lipoxygenase. J BIOL CHEM , 282 (28) 20151 - 20163. 10.1074/jbc.M611776200. Gold open access

Abstract

12/15-Lipoxygenase (LOX) mediates immune-regulatory activities not accounted for by its known free acid eicosanoids, suggesting that additional lipids may be generated by activated cells. To characterize novel LOX-derived lipids, a lipidomic approach was utilized. Ionophore-activated interleukin-4-treated human peripheral monocytes generated up to 10-fold more esterified 15-hydroxyeicosatetraenoic acid (15-HETE) than free in a phosphatidylinositol 3-kinase- and protein kinase C-sensitive manner. Precursor scanning electrospray ionization/tandem spectroscopy form/z 319 ( HETE, [M-H](-)) showed 4 ions at m/z 738, 764, 766, and 782 that were identified using tandem spectroscopy and MS3 as specific diacyl and plasmalogen 15-HETE phosphatidylethanolamines. Using (H2O)-O-18 water, the compounds were shown to form by direct oxidation of endogenous phosphatidylethanolamine (PE) by 15-LOX, with PE being the preferred phospholipid pool containing 15-HETE. Similarly, human platelets generated 4 analogous PE lipids that contained 12-HETE and increased significantly in response to ionophore, collagen, or convulxin. These products were retained in the cells, in contrast to free acids, which are primarily secreted. Precursor scanning of platelet extracts for the major platelet-derived prostanoid, thromboxane B2 (m/z 369.2), did not reveal PE esters, indicating that this modification is restricted to the LOX pathway. In summary, we show formation of PE-esterified HETEs in immune cells that may contribute to LOX signaling in inflammation.

Type: Article
Title: Activated platelets and monocytes generate four hydroxyphosphatidylethanolamines via lipoxygenase
Open access status: An open access publication
DOI: 10.1074/jbc.M611776200
Keywords: LIVER EPITHELIAL-CELLS, 15-HYDROXYEICOSATETRAENOIC ACID, 12(S)-HYDROXYEICOSATETRAENOIC ACID, SELECTIVE INCORPORATION, SIGNALING PATHWAY, GLYCOPROTEIN-VI, RECEPTOR-GAMMA, KNOCKOUT MICE, FATTY-ACIDS, PHOSPHOLIPIDS
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
URI: http://discovery.ucl.ac.uk/id/eprint/168225
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