Saturated-efferocytosis generates pro-resolving CD11b low macrophages: modulation by resolvins and glucocorticoids.

Saturated-efferocytosis generates pro-resolving CD11b low macrophages: modulation by resolvins and glucocorticoids.
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DOI:
10.1002/eji.201040801
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发表时间:
2011-02
影响因子:
5.4
通讯作者:
Ariel, Amiram
Ariel, Amiram
中科院分区:
医学3区
文献类型:
--
作者:
Schif-Zuck, Sagie;Gross, Nufar;Assi, Simaan;Rostoker, Ran;Serhan, Charles N.;Ariel, Amiram

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在炎症消退阶段,凋亡的白细胞被巨噬细胞以非炎性方式胞吞,导致对细菌部分的反应减弱和抗炎细胞因子的产生。补体受体 3 (CR3) 和促溶解脂质介质促进巨噬细胞吞噬凋亡白细胞。在这里,我们提供了在小鼠腹膜炎消退过程中体内出现促消退 CD11blow 巨噬细胞的证据。这些巨噬细胞在功能蛋白表达谱以及促溶解特性方面与大多数腹膜巨噬细胞不同,例如凋亡白细胞吞噬、对 TLR 配体漠不关心以及迁移至淋巴器官。值得注意的是,我们还发现巨噬细胞在与离体凋亡细胞相互作用后从 CD11bhigh 表型转变为 CD11blow 表型。此外,我们发现促溶解脂质介质 resolvin (Rv) E1 和 RvD1 以及糖皮质激素地塞米松 (Dex) 在体内调节促溶解巨噬细胞功能。这种调节最终产生了一种新的促分解功能,即减少 CD11blow 巨噬细胞生成所需的凋亡白细胞摄取需求。这些新的表型和分子途径标记定义了新的饱足巨噬细胞。因此,我们认为令人满意的胞吞作用会产生 CD11blow 巨噬细胞,这对于完全非炎性抑制炎症因子和终止急性炎症至关重要。
During the resolution phase of inflammation apoptotic leukocytes are efferocytosed by macrophages in a nonphlogistic fashion that results in diminished responses to bacterial moieties and production of anti-inflammatory cytokines. Complement receptor 3 (CR3) and pro-resolving lipid mediators promote the engulfment of apoptotic leukocytes by macrophages. Here, we present evidence for the emergence of pro-resolving, CD11blow macrophages in vivo during the resolution of murine peritonitis. These macrophages are distinct from the majority of peritoneal macrophages in terms of their functional protein expression profile, as well as pro-resolving properties, such as apoptotic leukocyte engulfment, indifference to TLR ligands, and emigration to lymphoid organs. Notably, we also found macrophages convert from the CD11bhigh to the CD11blow phenotype upon interaction with apoptotic cells ex vivo. In addition, we found that the pro-resolving lipid mediators resolvin (Rv) E1 and RvD1, and the glucocorticoid dexamethasone (Dex) regulated pro-resolving macrophage functions in vivo. This regulation culminated in a novel pro-resolving function, namely reducing the apoptotic leukocyte ingestion requirement for CD11blow macrophage generation. These new phenotype and molecular pathway markers define the new satiated-macrophage. Thus, we suggest that satisfying-efferocytosis generates CD11blow macrophages that are essential for complete non-phlogistic containment of inflammatory agents and the termination of acute inflammation.
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