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DioxolaneA3-phosphatidylethanolamines are generated by human platelets and stimulate neutrophil integrin expression

Aldrovandi, MacEler, Hinz, Christine, Lauder, Sarah N, Podmore, Helen, Hornshaw, Martin, Slatter, David A, Tyrrell, Victoria J, Clark, Stephen R, Marnett, Lawrence J., Collins, Peter W, Murphy, Robert C and O'Donnell, Valerie B 2017. DioxolaneA3-phosphatidylethanolamines are generated by human platelets and stimulate neutrophil integrin expression. Redox Biology 11 , pp. 663-672. 10.1016/j.redox.2017.01.001

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Activated platelets generate an eicosanoid proposed to be 8-hydroxy-9,10-dioxolane A3 (DXA3). Herein, we demonstrate that significant amounts of DXA3 are rapidly attached to phosphatidylethanolamine (PE) forming four esterified eicosanoids, 16:0p, 18:0p, 18:1p and 18:0a/DXA3-PEs that can activate neutrophil integrin expression. These lipids comprise the majority of DXA3 generated by platelets, are formed in ng amounts (24.3 ± 6.1 ng/2×108) and remain membrane bound. Pharmacological studies revealed DXA3-PE formation involves cyclooxygenase-1 (COX), protease-activated receptors (PAR) 1 and 4, cytosolic phospholipase A2 (cPLA2), phospholipase C and intracellular calcium. They are generated primarily via esterification of newly formed DXA3, but can also be formed in vitro via co-oxidation of PE during COX-1 co-oxidation of arachidonate. All four DXA3-PEs were detected in human clots. Purified platelet DXA3-PE activated neutrophil Mac-1 expression, independently of its hydrolysis to the free eicosanoid. This study demonstrates the structures and cellular synthetic pathway for a family of leukocyte-activating platelet phospholipids generated on acute activation, adding to the growing evidence that enzymatic PE oxidation is a physiological event in innate immune cells.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Subjects: R Medicine > RS Pharmacy and materia medica
Uncontrolled Keywords: Eicosanoids; Platelets; Cyclooxygenase; Phospholipids; Mass spectrometry
Publisher: Elsevier
ISSN: 2213-2317
Date of First Compliant Deposit: 27 February 2017
Date of Acceptance: 3 January 2017
Last Modified: 06 May 2021 01:28

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