The lifespan of a neutrophil is short and limited by programmed cell death, followed by efferocytosis. When activated or exposed to insult, neutrophil death may be delayed to support neutrophil effector functions such as phagocytosis, cytokine release, and pathogen destruction by degranulation. However, neutrophils may also alter the type of cell death and thereby affect inflammatory responses and tissue remodeling. This review briefly introduces the various forms of neutrophil death including apoptosis, necrosis/necroptosis, and the formation of so-called "neutrophil extracellular traps" (NETs), and it summarizes the clearance of dead cells by efferocytosis. Importantly, distinct types of neutrophil death have been found to drive chronic inflammatory disorders and cancer. Thus, the tumor and its microenvironment can delay neutrophil apoptosis to exploit their pro-angiogenic and pro-metastatic properties. Conversely, neutrophils may enter rapid and suicidal cell death by forming extracellular traps, which are expelled DNA strands with neutrophil proteins. Components of these DNA-protein complexes such as histones, high-mobility group protein B1, or neutrophil elastase have been found to promote cancer cell proliferation, adhesion, migration, invasion, and thereby tumor metastasis. In other settings of chronic inflammatory disease such as gout, NETs have been found protective rather than detrimental, as they promoted the local degradation of pro-inflammatory cytokines by neutrophil proteases. Thus, the interaction of neutrophils with the tissue environment extends beyond the stage of the living cell and the type of neutrophil death shapes immune responses and tissue remodeling in health and disease.

中文翻译：

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中性粒细胞死亡在慢性炎症和癌症中的作用。

中性粒细胞的寿命很短，并且受到程序性细胞死亡和随后的胞吞作用的限制。当被激活或受到损伤时，中性粒细胞死亡可能会被延迟，以支持中性粒细胞效应功能，例如吞噬作用、细胞因子释放和脱颗粒破坏病原体。然而，中性粒细胞也可能改变细胞死亡的类型，从而影响炎症反应和组织重塑。本文简要介绍了中性粒细胞死亡的各种形式，包括细胞凋亡、坏死/坏死性凋亡以及所谓的“中性粒细胞胞外陷阱”（NET）的形成，并总结了通过胞吞作用清除死亡细胞的情况。重要的是，已发现不同类型的中性粒细胞死亡会导致慢性炎症性疾病和癌症。因此，肿瘤及其微环境可以延迟中性粒细胞凋亡，以利用其促血管生成和促转移特性。相反，中性粒细胞可能通过形成细胞外陷阱而进入快速的自杀性细胞死亡，这些陷阱与中性粒细胞蛋白一起排出 DNA 链。这些DNA-蛋白质复合物的成分，如组蛋白、高迁移率族蛋白B1或中性粒细胞弹性蛋白酶，被发现可促进癌细胞增殖、粘附、迁移、侵袭，从而促进肿瘤转移。在痛风等慢性炎症性疾病的其他情况下，NETs被发现具有保护作用而不是有害作用，因为它们促进中性粒细胞蛋白酶对促炎细胞因子的局部降解。因此，中性粒细胞与组织环境的相互作用超出了活细胞阶段，中性粒细胞死亡的类型决定了健康和疾病中的免疫反应和组织重塑。