School of Life Sciences, State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University, Beijing, PR China.
Traffic. 2010 May;11(5):675-87. doi: 10.1111/j.1600-0854.2010.01041.x.
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.
外泌体在许多生理和病理过程中发挥着重要作用。然而，外泌体与细胞的相互作用方式以及外泌体在受体细胞中的细胞内转运途径仍不清楚。在这里，我们报告来自 K562 或 MT4 细胞的外泌体被吞噬细胞内化的效率高于非吞噬细胞。大多数外泌体被观察到附着在非吞噬细胞的质膜上，而在吞噬细胞中，这些外泌体通过吞噬作用进入细胞。具体来说，它们与吞噬性聚苯乙烯羧酸修饰的乳胶珠（生物球）一起移动到吞噬体中，并进一步分类到吞噬溶酶体中。此外，外泌体的内化依赖于肌动蛋白细胞骨架和磷脂酰肌醇 3-激酶，并且可以通过 dynamin2 的敲低或 dynamin2 的显性负形式的过表达来抑制。此外，抗体预处理试验表明，tim4 而不是 tim1 参与了外泌体的摄取。我们还发现外泌体不会进入涉及小窝、巨胞饮和网格蛋白包被囊泡的内化途径。我们观察到外泌体通过吞噬作用进入细胞内，这对外泌体与细胞的相互作用和外泌体的细胞内转运途径具有重要意义。
