Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Med Hypotheses. 2011 Feb;76(2):293-5. doi: 10.1016/j.mehy.2010.10.027. Epub 2010 Nov 13.
Natural killer (NK) cells play critical roles in defense against tumors and viral infections. They exert their cytotoxic functions through the secretion of granules containing cytotoxic molecules, such as perforin and granzymes. These cytotoxic molecules are stored within dual-functional organelles, known as secretory lysosomes. Target cell recognition induces the formation of an "immunological synapse", between the NK cell and its target, into which cytotoxic granules release their contents. However the post-exocytosis regulation of the process is still largely unknown. Recent research and the data accumulated therefrom lead to new hypotheses that suggest that, not unlike synaptic vesicle recycling in neuronal terminals, NK cells also recycle not just their secretory lysosome membranes but their correlated cytotoxic molecules (perforin and granzymes). The newly endocytosed vesicles are used to replenish the "reserve pool" of vesicles for continued NK cell serial killings. These hypotheses, if proved to be correct, will significantly improve our understanding of NK cell cytotoxicity mechanisms and might even suggest new NK cell-based therapies that rely on NK serial killing abilities for overcoming tumors.
自然杀伤 (NK) 细胞在抵御肿瘤和病毒感染方面发挥着关键作用。它们通过分泌含有细胞毒性分子的颗粒来发挥其细胞毒性功能，例如穿孔素和颗粒酶。这些细胞毒性分子储存在称为分泌溶酶体的双功能细胞器中。靶细胞识别诱导 NK 细胞与其靶细胞之间形成“免疫突触”，在其中细胞毒性颗粒释放其内容物。然而，细胞外排后的调节过程在很大程度上仍然未知。最近的研究和积累的数据提出了新的假设，表明与神经元末梢中的突触小泡再循环不同，NK 细胞不仅可以再循环其分泌溶酶体膜，还可以再循环与其相关的细胞毒性分子（穿孔素和颗粒酶）。新内化的囊泡被用于补充用于持续 NK 细胞连续杀伤的“储备池”中的囊泡。如果这些假设被证明是正确的，将极大地提高我们对 NK 细胞细胞毒性机制的理解，甚至可能提出新的基于 NK 细胞的疗法，这些疗法依赖于 NK 细胞的连续杀伤能力来克服肿瘤。
