Novel cell death program leads to neutrophil extracellular traps.

Novel cell death program leads to neutrophil extracellular traps.
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DOI:
10.1083/jcb.200606027
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发表时间:
2007-01-15
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Zychlinsky A
Zychlinsky A
中科院分区:
其他
文献类型:
--
作者:
Fuchs TA;Abed U;Goosmann C;Hurwitz R;Schulze I;Wahn V;Weinrauch Y;Brinkmann V;Zychlinsky A

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神经细胞外陷阱(NETs)是由染色质和颗粒蛋白组成的细胞外结构,其结合并杀死微生物。我们发现,在刺激,中性粒细胞的核失去了它们的形状,和eu和异染色质均质化。随后,核被膜和颗粒膜崩解,允许NET成分混合。最后,NET随着细胞膜破裂而释放。这种细胞死亡过程不同于凋亡和坏死,并且取决于NADPH氧化酶产生活性氧(ROS)。慢性肉芽肿病患者携带NADPH氧化酶突变,不能激活细胞死亡途径或制造NET。这种新的ROS依赖性死亡允许中性粒细胞履行其抗菌功能,甚至超过其寿命。
Neutrophil extracellular traps (NETs) are extracellular structures composed of chromatin and granule proteins that bind and kill microorganisms. We show that upon stimulation, the nuclei of neutrophils lose their shape, and the eu- and heterochromatin homogenize. Later, the nuclear envelope and the granule membranes disintegrate, allowing the mixing of NET components. Finally, the NETs are released as the cell membrane breaks. This cell death process is distinct from apoptosis and necrosis and depends on the generation of reactive oxygen species (ROS) by NADPH oxidase. Patients with chronic granulomatous disease carry mutations in NADPH oxidase and cannot activate this cell-death pathway or make NETs. This novel ROS-dependent death allows neutrophils to fulfill their antimicrobial function, even beyond their lifespan.