Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Peoples Republic of China.
Cell Biol Int. 2012 Feb;36(2):223-8. doi: 10.1042/CBI20110242.
When encountering target cells, NK (natural killer) cells exocytose Pfn (perforin) and granzyme B to kill challengers. We previously reported that granzyme B is recycled and reused by NK cells via clathrin-dependent endocytosis. However, whether Pfn, a main secretory vesicle content, indispensible to granzyme B killing, undergoes endocytosis remains unknown. We demonstrate that Pfn is recaptured by early endosomes of NK cells via a clathrin-dependent endocytosis after target cell stimulation. Inhibition of clathrin-dependent endocytosis significantly attenuated the cytotoxicity of NK cells. The data suggest that the recovery of Pfn contributes to the cytotoxicity of NK cells. The assay of endocytosis of lytic molecule presents a particular focus for exploring the mechanism of abnormal cytotoxicity of NK cells.
当遇到靶细胞时，NK（自然杀伤）细胞通过胞吐作用释放穿孔素（Pfn）和颗粒酶 B 来杀死挑战者。我们之前报道过，颗粒酶 B 通过网格蛋白依赖性内吞作用被 NK 细胞回收和再利用。然而，作为颗粒酶 B 杀伤所必需的主要分泌囊泡内容物的穿孔素是否经历内吞作用尚不清楚。我们证明，在靶细胞刺激后，穿孔素通过网格蛋白依赖性内吞作用被 NK 细胞的早期内体重新捕获。网格蛋白依赖性内吞作用的抑制显著减弱了 NK 细胞的细胞毒性。数据表明，穿孔素的回收有助于 NK 细胞的细胞毒性。裂解分子内吞作用的测定为探索 NK 细胞异常细胞毒性的机制提供了一个特别关注的焦点。
