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

被引:16
作者
Aldrovandi, Maceler [1 ,2 ]
Hinz, Christine [1 ,2 ]
Lauder, Sarah N. [1 ,2 ]
Podmore, Helen [4 ]
Hornshaw, Martin [4 ]
Slatter, David A. [1 ,2 ]
Tyrrell, Victoria J. [1 ,2 ]
Clark, Stephen R. [1 ,2 ]
Marnett, Lawrence J. [5 ]
Collins, Peter W. [1 ,2 ]
Murphy, Robert C. [3 ]
O'Donnell, Valerie B. [1 ,2 ]
机构
[1] Cardiff Univ, Sch Med, Syst Immun Res Inst, Cardiff CF14 4XN, S Glam, Wales
[2] Cardiff Univ, Sch Med, Inst Infect & Immun, Cardiff CF14 4XN, S Glam, Wales
[3] Univ Colorado Denver, Dept Pharmacol, Aurora, CO 80045 USA
[4] Boundary Way, Thermo Fisher Sci, Stafford House, Hemel Hempstead HP2 7GE, England
[5] Vanderbilt Inst Chem Biol, Ctr Mol Toxicol, Vanderbilt Ingram Canc Ctr, Nashville, TN USA
来源
REDOX BIOLOGY | 2017年 / 11卷
基金
英国惠康基金; 美国国家卫生研究院;
关键词
Eicosanoids; Platelets; Cyclooxygenase; Phospholipids; Mass spectrometry; ACTIVATED HUMAN PLATELETS; ESTERIFIED EICOSANOIDS; PHOSPHOLIPIDS; FERROPTOSIS;
D O I
10.1016/j.redox.2017.01.001
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Activated platelets generate an eicosanoid proposed to be 8-hydroxy-9,10-dioxolane A3 (DXA(3)). Herein, we demonstrate that significant amounts of DXA(3) are rapidly attached to phosphatidylethanolamine (PE) forming four esterified eicosanoids, 16:0p, 18:0p, 18:1p and 18:0a/DXA(3)-PEs that can activate neutrophil integrin expression. These lipids comprise the majority of DXA(3) generated by platelets, are formed in ng amounts (24.3 +/- 6.1 ng/2x10(8)) and remain membrane bound. Pharmacological studies revealed DXA(3)-PE formation involves cyclooxygenase-1 (COX), protease-activated receptors (PAR) 1 and 4, cytosolic phospholipase A2 (cPLA(2)), phospholipase C and intracellular calcium. They are generated primarily via esterification of newly formed DXA(3), but can also be formed in vitro via co-oxidation of PE during COX-1 co-oxidation of arachidonate. All four DXA(3)-PEs were detected in human clots. Purified platelet DXA(3)-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.
引用
收藏
页码:663 / 672
页数:10
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