Rapid reuptake of granzyme B leads to emperitosis: an apoptotic cell-in-cell death of immune killer cells inside tumor cells

被引:55
作者
Wang, S. [1 ,2 ,3 ,4 ]
He, M-f [1 ,2 ,3 ]
Chen, Y-h [1 ,2 ,3 ]
Wang, M-y [5 ]
Yu, X-m [6 ]
Bai, J. [1 ,2 ,3 ]
Zhu, H-y [1 ,2 ,3 ]
Wang, Y-y [1 ,2 ,3 ]
Zhao, H. [1 ,2 ,3 ]
Mei, Q. [1 ,2 ,3 ]
Nie, J. [1 ,2 ,3 ]
Ma, J. [1 ,2 ,3 ]
Wang, J-f [1 ,2 ,3 ]
Wen, Q. [7 ]
Ma, L. [7 ]
Wang, Y. [6 ]
Wang, X-n [1 ,2 ,3 ,8 ]
机构
[1] Chinese Peoples Liberat Army Gen Hosp, Inst Life Sci, Beijing 100853, Peoples R China
[2] S China Univ Technol, State Key Lab Kidney Dis, Guangzhou, Guangdong, Peoples R China
[3] Prov Key Lab Biotechnol, Guangzhou 510006, Guangdong, Peoples R China
[4] Guangzhou Med Univ, Affiliated Hosp 2, Guangzhou 510260, Guangdong, Peoples R China
[5] Wenzhou Med Univ, Sch Ophthalmol & Optometry, Wenzhou 325000, Peoples R China
[6] Shanghai Jiao Tong Univ, Shanghai Inst Immunol, Dept Immunol & Microbiol, Inst Med Sci,Sch Med, Shanghai 200025, Peoples R China
[7] Southern Med Univ, Inst Mol Immunol, Sch Biotechnol, Guangzhou 510515, Guangdong, Peoples R China
[8] Fudan Univ, Sch Life Sci, Shanghai 200433, Peoples R China
来源
CELL DEATH & DISEASE | 2013年 / 4卷
基金
中国国家自然科学基金;
关键词
apoptotic cell-in-cell death; emperitosis; immune cytotoxic cells; granzyme B; vacuole formation; CANNIBALISM; ACTIVATION; PROTEASE; LYMPHOCYTES; MECHANISM; PREVENTS; PERFORIN; ENTOSIS; RELEASE; SYSTEM;
D O I
10.1038/cddis.2013.352
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
A cell-in-cell process refers to the invasion of one living cell into another homotypic or heterotypic cell. Different from non-apoptotic death processes of internalized cells termed entosis or cannibalism, we previously reported an apoptotic cell-incell death occurring during heterotypic cell-in-cell formation. In this study, we further demonstrated that the apoptotic cell-in-cell death occurred only in internalized immune killer cells expressing granzyme B (GzmB). Vacuole wrapping around the internalized cells inside the target cells was the common hallmark during the early stage of all cell-in-cell processes, which resulted in the accumulation of reactive oxygen species and subsequent mitochondrial injury of encapsulated killer or non-cytotoxic immune cells. However, internalized killer cells mediated rapid bubbling of the vacuoles with the subsequent degranulation of GzmB inside the vacuole of the target cells and underwent the reuptake of GzmB by killer cells themselves. The confinement of GzmB inside the vacuole surpassed the lysosome-mediated cell death occurring in heterotypic or homotypic entosis processes, resulting in a GzmB-triggered caspase-dependent apoptotic cell-in-cell death of internalized killer cells. On the contrary, internalized killer cells from GzmB-deficient mice underwent a typical non-apoptotic entotic cell-in-cell death similar to that of non-cytotoxic immune cells or tumor cells. Our results thus demonstrated the critical involvement of immune cells with cytotoxic property in apoptotic cell-in-cell death, which we termed as emperitosis taken from emperipolesis and apoptosis. Whereas entosis or cannibalism may serve as a feed-on mechanism to exacerbate and nourish tumor cells, emperitosis of immune killer cells inside tumor cells may serve as an in-cell danger sensation model to prevent the killing of target cells from inside, implying a unique mechanism for tumor cells to escape from immune surveillance.
引用
收藏
页码:e856 / e856
页数:11
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