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Perforin is recaptured by natural killer cells following target cells stimulation for cytotoxicity

Authors

  • Lei Wang,

    1. Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Peoples Republic of China
    2. Institute of Laboratory Medicine, Hubei University of Chinese Medicine, No. 1, Huangjia Lake West Road, Wuhan, 430065, Peoples Republic of China
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  • Rulin Sun,

    1. Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Peoples Republic of China
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  • Pan Li,

    1. Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Peoples Republic of China
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  • Yang Han,

    1. Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Peoples Republic of China
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  • Ping Xiong,

    1. Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Peoples Republic of China
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  • Yong Xu,

    1. Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Peoples Republic of China
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  • Min Fang,

    1. Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Peoples Republic of China
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  • Zheng Tan,

    1. Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Peoples Republic of China
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  • Fang Zheng,

    Corresponding author
    1. Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Peoples Republic of China
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  • Feili Gong

    Corresponding author
    1. Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Peoples Republic of China
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Correspondence may be addressed to either of the authors (email zhengfangtj@yahoo.com or flgong@163.com).

Abstract

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.

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