Cellular Internalization of Exosomes Occurs Through Phagocytosis
Cellular Internalization of Exosomes Occurs Through Phagocytosis
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外泌体的细胞内化通过吞噬作用发生
DOI：
10.1111/j.1600-0854.2010.01041.x
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发表时间：
2010-05-01
期刊：
影响因子：
4.5
通讯作者：
Sui, Sen-Fang
中科院分区：
文献类型：
--
作者：
Feng, Du;Zhao, Wen-Long;Sui, Sen-Fang
外切体在许多生理和病理过程中起着重要的作用。然而，外切体与细胞的相互作用方式以及外切体在受体细胞中的细胞内转运途径尚不清楚。在这里，我们报告了来自K562或MT4细胞的外切体被吞噬细胞比非吞噬细胞更有效地内化。大多数外切体附着在非吞噬细胞的质膜上，而在吞噬细胞中，这些外切体是通过吞噬进入的。具体地说，它们与吞噬聚苯乙烯羧酸盐修饰的乳胶珠(生物球)一起移动到吞噬小体上，并进一步分类为吞噬小体。此外，外切体的内化依赖于肌动蛋白细胞骨架和磷脂酰肌醇3-激酶，并且可以被Dynamin2的敲除或显性-负性形式的Dynamin2的过度表达所抑制。此外，抗体预处理分析表明，tim4而不是tim1参与了外切体的摄取。我们还发现，外切体没有进入内化途径，包括小凹、巨噬细胞吞噬和笼蛋白包裹的小泡。我们观察到细胞通过吞噬作用摄取外切体，这对外切体与细胞之间的相互作用和外切体在细胞内的运输途径具有重要的意义。
Exosomes play important roles in many physiological and pathological processes. However, the exosome-cell interaction mode and the intracellular trafficking pathway of exosomes in their recipient cells remain unclear. Here, we report that exosomes derived from K562 or MT4 cells are internalized more efficiently by phagocytes than by non-phagocytic cells. Most exosomes were observed attached to the plasma membrane of non-phagocytic cells, while in phagocytic cells these exosomes were found to enter via phagocytosis. Specifically, they moved to phagosomes together with phagocytic polystyrene carboxylate-modified latex beads (biospheres) and were further sorted into phagolysosomes. Moreover, exosome internalization was dependent on the actin cytoskeleton and phosphatidylinositol 3-kinase, and could be inhibited by the knockdown of dynamin2 or overexpression of a dominant-negative form of dynamin2. Further, antibody pretreatment assays demonstrated that tim4 but not tim1 was involved in exosomes uptake. We also found that exosomes did not enter the internalization pathway involving caveolae, macropinocytosis and clathrin-coated vesicles. Our observation that the cellular uptake of exosomes occurs through phagocytosis has important implications for exosome-cell interactions and the exosome intracellular trafficking pathway.