DioxolaneA3-phosphatidylethanolamines are generated by human platelets and stimulate neutrophil integrin expression.
DioxolaneA3-phosphatidylethanolamines are generated by human platelets and stimulate neutrophil integrin expression.
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DOI：
10.1016/j.redox.2017.01.001
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发表时间：
2017-04
期刊：
影响因子：
11.4
通讯作者：
O'Donnell VB
中科院分区：
文献类型：
--
作者：
Aldrovandi M;Hinz C;Lauder SN;Podmore H;Hornshaw M;Slatter DA;Tyrrell VJ;Clark SR;Marnett LJ;Collins PW;Murphy RC;O'Donnell VB
活化的血小板产生一种被认为是8-羟基-9,10-二恶烷A3 （DXA3）的类二十烷。在这里，我们证明了大量的DXA3快速附着在磷脂酰乙醇胺（PE）上，形成四种酯化的二十烷酸，16:0p, 18:0p， 18:1p和18:0a/DXA3- pes，可以激活中性粒细胞整合素的表达。这些脂质构成了血小板生成的DXA3的大部分，形成量为ng(24.3±6.1 ng/2×108)，并保持膜结合。药理研究表明，DXA3-PE的形成涉及环氧化酶-1 （COX）、蛋白酶活化受体（PAR） 1和4、胞质磷脂酶A2 （cPLA2）、磷脂酶C和细胞内钙。它们主要通过新形成的DXA3的酯化反应生成，但也可以在体外通过花生四烯酸的COX-1共氧化过程中PE的共氧化生成。四种dxa3 - pe均在人血块中检测到。纯化的血小板DXA3-PE激活中性粒细胞Mac-1的表达，独立于其水解为游离类二十烷。本研究揭示了急性活化时产生的白细胞活化血小板磷脂家族的结构和细胞合成途径，进一步证明酶促PE氧化是先天免疫细胞中的生理事件。描述了四种酶氧化磷脂，称为血小板中的DXA3-PE。由环氧丙烷-1氧化花生四烯酸酯生成DXA3-PE，然后酯化成PE。DXA3-PE的形成需要钙、磷脂酶C和磷脂酶A2。从血小板中纯化的DXA3-PEs可激活中性粒细胞Mac-1的表达。
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. Four enzymatically oxidized phospholipids are described, termed DXA3-PE in platelets. DXA3-PE forms by COX-1 oxidation of arachidonate, then esterification into PE. DXA3-PE formation requires calcium, phospholipase C and phospholipase A2. DXA3-PEs purified from platelets activates neutrophil Mac-1 expression.