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中性粒细胞死亡——远不止表面所见。

Neutrophil death-more than meets the eye.

作者信息

Hsu Alan Y, Huang Qingxiang, Liu Fei, Balasubramanian Arumugam, Luo Hongbo R

机构信息

Department of Pathology, Dana-Farber/Harvard Cancer Center, PhD Program in Immunology, Harvard Medical School, Boston, MA; Department of Pathology, Mass General Brigham, Boston, MA.

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.

出版信息

Exp Hematol. 2025 Jul 11;150:104857. doi: 10.1016/j.exphem.2025.104857.


DOI:10.1016/j.exphem.2025.104857
PMID:40653261
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12376072/
Abstract

Neutrophils play an indispensable role in the innate immune system as the body's first line of defense against pathogens. These highly specialized cells are rapidly recruited to infection sites, where they execute a variety of critical functions essential for pathogen clearance. These functions include phagocytosis, degranulation, the release of antimicrobial peptides and reactive oxygen species (ROS), as well as the formation of neutrophil extracellular traps (NETs), which serve to directly neutralize pathogens or restrict their spread. Despite their abundance-accounting for 40%-70% of total white blood cells in human circulation, neutrophils have a relatively short lifespan. To maintain immune homeostasis, approximately 1 billion neutrophils per kilogram of body weight are produced and cleared each day, a highly regulated and energy-intensive process. Neutrophil death is a highly heterogeneous process, with neutrophils undergoing different forms of cell death depending on the stimuli, signaling, and microenvironment. Even during aging or cell death, neutrophils continue to exert significant effects on the immune landscape. In this review, we discuss the dynamics of neutrophil turnover during homeostasis and inflammation, the diversity of mechanisms governing their death, and the multifaceted roles of neutrophils in modulating the immune environment both during and after their demise.

摘要

中性粒细胞作为机体抵御病原体的第一道防线,在固有免疫系统中发挥着不可或缺的作用。这些高度特化的细胞会迅速被招募到感染部位,在那里它们执行各种清除病原体所必需的关键功能。这些功能包括吞噬作用、脱颗粒、释放抗菌肽和活性氧(ROS),以及形成中性粒细胞胞外陷阱(NETs),其作用是直接中和病原体或限制其传播。尽管中性粒细胞数量众多,占人体循环中白细胞总数的40%-70%,但其寿命相对较短。为维持免疫稳态,每天每千克体重会产生并清除约10亿个中性粒细胞,这是一个高度受调控且耗能的过程。中性粒细胞死亡是一个高度异质性的过程,中性粒细胞会根据刺激、信号传导和微环境经历不同形式的细胞死亡。即使在衰老或细胞死亡期间,中性粒细胞仍会对免疫格局产生重大影响。在这篇综述中,我们讨论了稳态和炎症过程中中性粒细胞更新的动态变化、其死亡调控机制的多样性,以及中性粒细胞在其死亡期间和之后调节免疫环境的多方面作用。

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本文引用的文献

[1]
Neutrophil-derived vesicles control complement activation to facilitate inflammation resolution.

Cell. 2025-3-20

[2]
NLRP1-dependent activation of Gasdermin D in neutrophils controls cutaneous leishmaniasis.

PLoS Pathog. 2024-9

[3]
Palmitoylation at a conserved cysteine residue facilitates gasdermin D-mediated pyroptosis and cytokine release.

Proc Natl Acad Sci U S A. 2024-7-16

[4]
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Nature. 2024-6

[5]
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Nat Cell Biol. 2024-5

[6]
The palmitoylation of gasdermin D directs its membrane translocation and pore formation during pyroptosis.

Sci Immunol. 2024-4-12

[7]
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J Leukoc Biol. 2024-9-2

[8]
Deterministic reprogramming of neutrophils within tumors.

Science. 2024-1-12

[9]
Gasdermin E dictates inflammatory responses by controlling the mode of neutrophil death.

Nat Commun. 2024-1-9

[10]
NET formation is a default epigenetic program controlled by PAD4 in apoptotic neutrophils.

Sci Adv. 2023-12-22

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