Perforin triggers a plasma membrane-repair response that facilitates CTL induction of apoptosis
Perforin triggers a plasma membrane-repair response that facilitates CTL induction of apoptosis
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DOI：
10.1016/j.immuni.2005.08.001
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发表时间：
2005-09-01
期刊：
影响因子：
32.4
通讯作者：
Lieberman, J
中科院分区：
文献类型：
--
作者：
Keefe, D;Shi, LF;Lieberman, J
穿孔素递送颗粒酶以诱导靶细胞凋亡。在高浓度下，穿孔素在质膜中多聚形成孔。然而，颗粒酶是否通过膜孔进入靶细胞尚不确定。在这里，我们发现生理相关浓度的穿孔素和细胞介导的裂解过程中在靶细胞膜上产生孔，暂时允许Ca2+和小染料进入细胞。 Ca2+ 通量触发受伤的膜修复反应，其中包括溶酶体和内体在内的内部囊泡捐赠其膜来重新密封受损的膜。穿孔素还引发颗粒酶快速内吞到大的 EEA-1 染色囊泡中。通过触发修复反应来恢复靶细胞膜的完整性对于遭受细胞毒性T淋巴细胞攻击的靶细胞来说是必要的，以避免坏死并经历较慢的程序性细胞死亡过程。因此，靶细胞在细胞介导的死亡过程中积极参与决定其自身的命运。
Perforin delivers granzymes to induce target-cell apoptosis. At high concentrations, perforin multimerizes in the plasma membrane to form pores. However, whether granzymes enter target cells via membrane pores is uncertain. Here we find that perforin at physiologically relevant concentrations and during cell-mediated lysis creates pores in the target-cell membrane, transiently allowing Ca2+ and small dyes into the cell. The Ca2+ flux triggers a wounded membrane-repair response in which internal vesicles, including lysosomes and endosomes, donate their membranes to reseal the damaged membrane. Perforin also triggers the rapid endocytosis of granzymes into large EEA-1-staining vesicles. The restoration of target-cell membrane integrity by triggering the repair response is necessary for target cells subjected to cytotoxic T lymphocyte attack to avoid necrosis and undergo the slower process of programmed cell death. Thus, the target cell actively participates in determining its own fate during cell-mediated death.