Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Cell Mol Life Sci. 2010 Sep;67(18):3197-208. doi: 10.1007/s00018-010-0377-8. Epub 2010 May 7.
When they recognize a target cell, natural killer (NK) cells mount an attack to kill the target by exerting their cytotoxicity via the exocytosis of cytotoxic granules. Although the details of this process (which includes the movement of cytotoxic granules in the immune synapse and their fusion with the plasma membrane, releasing granzymes and perforin into the synaptic cleft) are relatively better understood, the post-exocytosis regulation of the process is still largely unknown. Here we show that a clathrin-dependent endocytosis stimulated by target cell occurs in NK92 cell line, which is closely correlated with granzyme B recovery. Inhibition of the endocytosis significantly attenuates the cytotoxicity of NK92 cells. The NK cell recovery of its released effector molecules, in turn, suggests that endocytosis may well play a key role in the post exocytosis regulation of immune cells.
当自然杀伤 (NK) 细胞识别靶细胞时,通过细胞毒性颗粒的胞吐作用发挥细胞毒性来攻击并杀死靶细胞。尽管这个过程的细节(包括细胞毒性颗粒在免疫突触中的运动及其与质膜融合,将颗粒酶和穿孔素释放到突触间隙中)相对更容易理解,但该过程的胞吐后调节仍然很大程度上未知。在这里,我们表明 NK92 细胞系中发生了由靶细胞刺激的网格蛋白依赖性内吞作用,这与颗粒酶 B 的恢复密切相关。内吞作用的抑制显著减弱了 NK92 细胞的细胞毒性。释放的效应分子的 NK 细胞恢复,这反过来表明内吞作用可能在免疫细胞的胞吐后调节中发挥关键作用。