Phosphatidylethanolamine-esterified eicosanoids in the mouse: tissue localization and inflammation-dependent formation in Th-2 disease.
Phosphatidylethanolamine-esterified eicosanoids in the mouse: tissue localization and inflammation-dependent formation in Th-2 disease.
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DOI：
10.1074/jbc.m109.021634
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发表时间：
2009-08-07
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影响因子：
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通讯作者：
O'Donnell VB
中科院分区：
文献类型：
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作者：
Morgan AH;Dioszeghy V;Maskrey BH;Thomas CP;Clark SR;Mathie SA;Lloyd CM;Kühn H;Topley N;Coles BC;Taylor PR;Jones SA;O'Donnell VB
在这项研究中，发现来自幼稚灌洗的小鼠腹腔巨噬细胞产生四种含有12-羟基二十碳四烯酸（12-HETE）的磷脂。它们包含三种缩醛磷脂和一种二酰基磷脂酰乙醇胺（PE）（16：0 p、18：1 p、18：0 p和18：0a在sn-1），并且在12/15-脂氧合酶（12/15-LOX）缺陷小鼠的巨噬细胞中不存在。它们是响应钙动员而急性产生的，主要与细胞相关，并在质膜外部检测到。未处理灌洗液中12-HETE-PE的水平与游离12-HETE的水平在相似的范围内（酯化与游离分别为5.5 ± 0.2 ng或18.5 ± 1.03 ng/灌洗液）。在健康小鼠中，在腹膜腔、腹膜、淋巴结和肠中发现12/15-LOX衍生的12-HETE-PE，其分布与12/15-LOX衍生的12-HETE相似。12-HETE-PE的体内产生发生在与白细胞介素-4/白细胞介素-13表达相关的鼠肺部炎症的Th 2依赖性模型中。相反，在由活细菌或细菌产物介导的Toll受体依赖性腹膜炎中，12-HETE-PE在急性期迅速清除，然后在消退期间重新出现。人同系物18：0a/15-HETE-PE抑制人单核细胞响应脂多糖产生细胞因子。总之，一个新的家庭的脂质介质产生的小鼠巨噬细胞在Th 2炎症被确定和结构特征。这些研究表明，炎症中12/15-LOX产生的脂质涉及酯化类二十烷酸的形成。
In this study, murine peritoneal macrophages from naïve lavage were found to generate four phospholipids that contain 12-hydroxyeicosatetraenoic acid (12-HETE). They comprise three plasmalogen and one diacyl phosphatidylethanolamines (PEs) (16:0p, 18:1p, 18:0p, and 18:0a at sn-1) and are absent in macrophages from 12/15-lipoxygenase (12/15-LOX)-deficient mice. They are generated acutely in response to calcium mobilization, are primarily cell-associated, and are detected on the outside of the plasma membrane. Levels of 12-HETE-PEs in naïve lavage are in a similar range to those of free 12-HETE (5.5 ± 0.2 ng or 18.5 ± 1.03 ng/lavage for esterified versus free, respectively). In healthy mice, 12/15-LOX-derived 12-HETE-PEs are found in the peritoneal cavity, peritoneal membrane, lymph node, and intestine, with a similar distribution to 12/15-LOX-derived 12-HETE. In vivo generation of 12-HETE-PEs occurs in a Th2-dependent model of murine lung inflammation associated with interleukin-4/interleukin-13 expression. In contrast, in Toll receptor-dependent peritonitis mediated either by live bacteria or bacterial products, 12-HETE-PEs are rapidly cleared during the acute phase then reappear during resolution. The human homolog, 18:0a/15-HETE-PE inhibited human monocyte generation of cytokines in response to lipopolysaccharide. In summary, a new family of lipid mediators generated by murine macrophages during Th2 inflammation are identified and structurally characterized. The studies suggest a new paradigm for lipids generated by 12/15-LOX in inflammation involving formation of esterified eicosanoids.