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Macrophages redirect phagocytosis by non-professional phagocytes and influence inflammation

机译：巨噬细胞通过非专业吞噬细胞重定向吞噬作用并影响炎症

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摘要

Professional phagocytes (such as macrophages(1)) and nonprofessional phagocytes(2-8) (such as epithelial cells) clear billions of apoptotic cells and particles on a daily basis(9). Although professional and non-professional macrophages reside in proximity in most tissues, whether they communicate with each other during cell clearance, and how this might affect inflammation, is not known(10). Here we show that macrophages, through the release of a soluble growth factor and microvesicles, alter the type of particles engulfed by non-professional phagocytes and influence their inflammatory response. During phagocytosis of apoptotic cells or in response to inflammation-associated cytokines, macrophages released insulin-like growth factor 1 (IGF-1). The binding of IGF-1 to its receptor on non-professional phagocytes redirected their phagocytosis, such that uptake of larger apoptotic cells was reduced whereas engulfment of microvesicles was increased. IGF-1 did not alter engulfment by macrophages. Macrophages also released microvesicles, whose uptake by epithelial cells was enhanced by IGF-1 and led to decreased inflammatory responses by epithelial cells. Consistent with these observations, deletion of IGF-1 receptor in airway epithelial cells led to exacerbated lung inflammation after allergen exposure. These genetic and functional studies reveal that IGF-1-and microvesicle-dependent communication between macrophages and epithelial cells can critically influence the magnitude of tissue inflammation in vivo.
机译：每天，专业吞噬细胞（例如巨噬细胞（1））和非专业吞噬细胞（2-8）（例如上皮细胞）清除数十亿的凋亡细胞和颗粒（9）。尽管专业和非专业巨噬细胞都位于大多数组织的附近，但它们在细胞清除过程中是否相互通讯以及这如何影响炎症尚不清楚（10）。在这里，我们显示巨噬细胞通过释放可溶性生长因子和微泡改变了非专业吞噬细胞吞噬的颗粒类型，并影响了它们的炎症反应。在凋亡细胞的吞噬作用或对炎症相关的细胞因子的反应期间，巨噬细胞释放了胰岛素样生长因子1（IGF-1）。 IGF-1与其非专业吞噬细胞上的受体的结合使它们的吞噬作用重新定向，从而减少了较大的凋亡细胞的摄取，而增加了微泡的吞噬。 IGF-1不会改变巨噬细胞的吞噬。巨噬细胞还释放微囊泡，IGF-1增强了微囊泡对上皮细胞的摄取，并导致上皮细胞的炎症反应减少。与这些观察结果一致，暴露于过敏原后，气道上皮细胞中IGF-1受体的缺失导致肺部炎症加剧。这些遗传和功能研究表明，巨噬细胞和上皮细胞之间的IGF-1和微囊泡依赖性通讯可严重影响体内组织炎症的程度。

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  • 来源
    《Nature》 |2016年第7630期|570-574|共5页
  • 作者

    Han Claudia Z.; Juncadella Ignacio J.; Kinchen Jason M.; Buckley Monica W.; Klibanov Alexander L.; Dryden Kelly; Onengut-Gumuscu Suna; Erdbruegger Uta; Turner Stephen D.; Shim Yun M.; Tung Kenneth S.; Ravichandran Kodi S.;

  • 作者单位

    Univ Virginia, Ctr Cell Clearance, Charlottesville, VA 22903 USA|Univ Virginia, Dept Microbiol Immunol & Canc Biol, Charlottesville, VA 22903 USA;

    Univ Virginia, Ctr Cell Clearance, Charlottesville, VA 22903 USA;

    Univ Virginia, Ctr Cell Clearance, Charlottesville, VA 22903 USA;

    Univ Virginia, Ctr Cell Clearance, Charlottesville, VA 22903 USA|Univ Virginia, Dept Microbiol Immunol & Canc Biol, Charlottesville, VA 22903 USA;

    Univ Virginia, Dept Med, Charlottesville, VA 22903 USA|Univ Virginia, Robert M Berne Cardiovasc Res Ctr, Charlottesville, VA 22903 USA;

    Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22903 USA;

    Univ Virginia, Div Endocrinol & Metab, Dept Med, Charlottesville, VA 22903 USA|Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22903 USA;

    Univ Virginia, Dept Med, Div Nephrol, Charlottesville, VA 22903 USA;

    Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA 22903 USA;

    Univ Virginia, Dept Med, Charlottesville, VA 22903 USA;

    Univ Virginia, Dept Med, Charlottesville, VA 22903 USA|Univ Virginia, Dept Pathol, Charlottesville, VA 22903 USA;

    Univ Virginia, Ctr Cell Clearance, Charlottesville, VA 22903 USA|Univ Virginia, Dept Microbiol Immunol & Canc Biol, Charlottesville, VA 22903 USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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