Cell and Developmental Biology Center, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, Bethesda, Maryland 20892, USA; email:
Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232.
Annu Rev Cell Dev Biol. 2020 Oct 6;36:191-218. doi: 10.1146/annurev-cellbio-020520-111016. Epub 2020 Jul 14.
Neutrophils are critical to innate immunity, including host defense against bacterial and fungal infections. They achieve their host defense role by phagocytosing pathogens, secreting their granules full of cytotoxic enzymes, or expelling neutrophil extracellular traps (NETs) during the process of NETosis. NETs are weblike DNA structures decorated with histones and antimicrobial proteins released by activated neutrophils. Initially described as a means for neutrophils to neutralize pathogens, NET release also occurs in sterile inflammation, promotes thrombosis, and can mediate tissue damage. To effectively manipulate this double-edged sword to fight a particular disease, researchers must work toward understanding the mechanisms driving NETosis. Such understanding would allow the generation of new drugs to promote or prevent NETosis as needed. While knowledge regarding the (patho)physiological roles of NETosis is accumulating, little is known about the cellular and biophysical bases of this process. In this review, we describe and discuss our current knowledge of the molecular, cellular, and biophysical mechanisms mediating NET release as well as open questions in the field.
中性粒细胞对于先天免疫至关重要，包括宿主抵御细菌和真菌感染的防御作用。它们通过吞噬病原体、分泌充满细胞毒性酶的颗粒，或在 NETosis 过程中排出中性粒细胞胞外陷阱 (NETs) 来实现其宿主防御作用。NETs 是由活化的中性粒细胞释放的带有组蛋白和抗菌蛋白的网状 DNA 结构。最初被描述为中性粒细胞中和病原体的一种手段，NET 释放也发生在无菌性炎症中，促进血栓形成，并可介导组织损伤。为了有效地操纵这把双刃剑来治疗特定疾病，研究人员必须努力理解驱动 NETosis 的机制。这种理解将允许生成新的药物，根据需要促进或预防 NETosis。虽然关于 NETosis 的（病理）生理作用的知识正在积累，但对于这个过程的细胞和生物物理基础知之甚少。在这篇综述中，我们描述和讨论了我们目前对介导 NET 释放的分子、细胞和生物物理机制的了解，以及该领域的开放性问题。
