在细胞焦亡过程中,细胞死亡和细胞裂解是可分离的事件。

Cell death and cell lysis are separable events during pyroptosis.

作者信息

DiPeso Lucian, Ji Daisy X, Vance Russell E, Price Jordan V

机构信息

Division of Immunology & Pathogenesis, Department of Molecular & Cell Biology, and Cancer Research Laboratory, University of California, Berkeley, CA, USA.

Howard Hughes Medical Institute, University of California, Berkeley, CA, USA.

出版信息

Cell Death Discov. 2017 Nov 13;3:17070. doi: 10.1038/cddiscovery.2017.70. eCollection 2017.

Abstract

Although much insight has been gained into the mechanisms by which activation of the inflammasome can trigger pyroptosis in mammalian cells, the precise kinetics of the end stages of pyroptosis have not been well characterized. Using time-lapse fluorescent imaging to analyze the kinetics of pyroptosis in individual murine macrophages, we observed distinct stages of cell death and cell lysis. Our data demonstrate that cell membrane permeability resulting from gasdermin D pore formation is coincident with the cessation of cell movement, loss of mitochondrial activity, and cell swelling, events that can be uncoupled from cell lysis. We propose a model of pyroptosis in which cell death can occur independently of cell lysis. The uncoupling of cell death from cell lysis may allow for better control of cytosolic contents upon activation of the inflammasome.

摘要

尽管对于炎性小体激活触发哺乳动物细胞焦亡的机制已有很多深入了解,但焦亡末期的精确动力学特征尚未得到很好的描述。利用延时荧光成像分析单个小鼠巨噬细胞中焦亡的动力学,我们观察到了细胞死亡和细胞裂解的不同阶段。我们的数据表明,由gasdermin D孔形成导致的细胞膜通透性与细胞运动停止、线粒体活性丧失和细胞肿胀同时发生,这些事件可与细胞裂解相分离。我们提出了一种焦亡模型,其中细胞死亡可以独立于细胞裂解而发生。细胞死亡与细胞裂解的分离可能允许在炎性小体激活时更好地控制胞质内容物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b03d/5682879/4fcd918fdb61/cddiscovery201770-f1.jpg

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