title: Perforin is recaptured by natural killer cells following target cells stimulation for cytotoxicity.
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.
authors: Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Peoples Republic of China.
authors: Lei
authors: L
authors: Wang
authors: Rulin
authors: R
authors: Sun
authors: Pan
authors: P
authors: Li
authors: Yang
authors: Y
authors: Han
authors: Ping
authors: P
authors: Xiong
authors: Yong
authors: Y
authors: Xu
authors: Min
authors: M
authors: Fang
authors: Zheng
authors: Z
authors: Tan
authors: Fang
authors: F
authors: Zheng
authors: Feili
authors: F
authors: Gong
mesh_terms: D002746:Chlorpromazine / Q000494:pharmacology; D002966:Clathrin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004705:Endocytosis / Q000187:drug effects; D011992:Endosomes / Q000378:metabolism; D053804:Granzymes / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D054353:Perforin / Q000032:analysis / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000378:metabolism
chemical_list: D002966:Clathrin; D018492:Dopamine Antagonists; D011500:Protein Synthesis Inhibitors; D034741:RNA, Small Interfering; D033921:Vesicular Transport Proteins; C093846:early endosome antigen 1; D054353:Perforin; D003513:Cycloheximide; D053804:Granzymes; D002746:Chlorpromazine