PGE(2) production at sites of tissue injury promotes an anti-inflammatory neutrophil phenotype and determines the outcome of inflammation resolution in vivo.
PGE(2) production at sites of tissue injury promotes an anti-inflammatory neutrophil phenotype and determines the outcome of inflammation resolution in vivo.
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DOI：
10.1126/sciadv.aar8320
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发表时间：
2018-09
期刊：
影响因子：
13.6
通讯作者：
Renshaw SA
中科院分区：
文献类型：
--
作者：
Loynes CA;Lee JA;Robertson AL;Steel MJ;Ellett F;Feng Y;Levy BD;Whyte MKB;Renshaw SA
炎症部位的中性粒细胞清除受巨噬细胞和中性粒细胞之间的脂质介质信号调控。
中性粒细胞是最早被募集到损伤或感染部位的免疫细胞，在那里它们发挥多种功能。完成其作用后，中性粒细胞必须从炎症部位清除——要么通过凋亡和胞葬作用，要么通过从伤口反向迁移——以恢复正常的组织内稳态。这些受到严格控制的中性粒细胞清除生理过程的紊乱可导致一系列炎症性疾病。我们利用一种体内斑马鱼模型来了解脂质介质产生在中性粒细胞清除中的作用。在没有巨噬细胞的情况下进行尾鳍截断后，中性粒细胞性炎症不会消退，这是因为依赖巨噬细胞的类花生酸前列腺素E2（PGE2）的处理缺失，而PGE2通过促进反向迁移驱动中性粒细胞清除。内源性PGE合酶基因的敲低揭示PGE2对中性粒细胞炎症的消退至关重要。此外，在损伤过程中，PGE2能够通过EP4受体发出信号，导致Alox12产生增加，并转向抗炎类花生酸信号传导。我们的数据证实了在炎症消退的体内模型中PGE2和LXA4（脂氧素A4）对中性粒细胞迁移的调控。该通路可能包含用于驱动慢性炎症性疾病中炎症消退的治疗靶点。
Neutrophil removal from inflammatory sites is regulated by lipid mediator signals between macrophages and neutrophils. Neutrophils are the first immune cells recruited to a site of injury or infection, where they perform many functions. Having completed their role, neutrophils must be removed from the inflammatory site—either by apoptosis and efferocytosis or by reverse migration away from the wound—for restoration of normal tissue homeostasis. Disruption of these tightly controlled physiological processes of neutrophil removal can lead to a range of inflammatory diseases. We used an in vivo zebrafish model to understand the role of lipid mediator production in neutrophil removal. Following tailfin amputation in the absence of macrophages, neutrophillic inflammation does not resolve, due to loss of macrophage-dependent handling of eicosanoid prostaglandin E2 (PGE2) that drives neutrophil removal via promotion of reverse migration. Knockdown of endogenous PGE synthase gene reveals PGE2 as essential for neutrophil inflammation resolution. Furthermore, PGE2 is able to signal through EP4 receptors during injury, causing an increase in Alox12 production and switching toward anti-inflammatory eicosanoid signaling. Our data confirm regulation of neutrophil migration by PGE2 and LXA4 (lipoxin A4) in an in vivo model of inflammation resolution. This pathway may contain therapeutic targets for driving inflammation resolution in chronic inflammatory disease.
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影响因子：
5.5
作者：
Ellett F;Elks PM;Robertson AL;Ogryzko NV;Renshaw SA
通讯作者：
Renshaw SA
影响因子：
9.2
作者：
Feng, Yi;Renshaw, Stephen;Martin, Paul
通讯作者：
Martin, Paul
影响因子：
15.9
作者：
Fadok, VA;Bratton, DL;Henson, PM
通讯作者：
Henson, PM
影响因子：
5.5
作者：
Buckley, Christopher D.;Ross, Ewan A.;Rainger, G. Ed
通讯作者：
Rainger, G. Ed
专门的促解决介质：感染和炎症的内源性调节剂。
DOI：
10.1038/nri.2015.4
发表时间：
2016-01
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Basil MC;Levy BD
通讯作者：
Levy BD