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  ORCID: https://orcid.org/0000-0002-6410-1324, Murphy, Robert C and O'Donnell, Valerie B ORCID: https://orcid.org/0000-0003-4089-8460
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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Abstract
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: | 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: | 31 Jan 2025 22:26 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/98590 |
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