Yadav Rachana, Momin Alfiya, Godugu Chandraiah
Department of Biological Sciences (Regulatory Toxicology), National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana, India.
Department of Biological Sciences (Regulatory Toxicology), National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana, India.
Int Immunopharmacol. 2023 Nov;124(Pt A):110846. doi: 10.1016/j.intimp.2023.110846. Epub 2023 Aug 25.
Neutrophils are the primary host innate immune cells defending against pathogens. One proposed mechanism by which neutrophils limit pathogen transmission is NETosis, which includes releasing the nuclear content into the cytosol by forming pores in the plasma membrane. The extrusion of cellular deoxyribonucleic acid (DNA) results in neutrophil extracellular traps (NETs) composed of nuclear DNA associated with histones and granule proteins. NETosis is driven by the enzyme PAD-4 (Peptidylarginine deiminase-4), which converts arginine into citrulline, leading to decondensation of chromatin, separation of DNA, and eventual extrusion. DNase is responsible for the breakdown of NETs. On the one hand, the release of DNase may interfere with the antibacterial effects of NETs; further, DNase may protect tissues from self-destruction caused by the increased release of NET under septic conditions. NETs in physiological quantities are expected to have a role in anti-infectious innate immune responses. In contrast, abnormally high concentrations of NETs in the body that are not adequately cleared by DNases can damage tissues and cause inflammation. Through several novel approaches, it is now possible to avoid the adverse effects caused by the continued release of NETs into the extracellular environment. In this review we have highlighted the basic mechanisms of NETosis, its significance in the pathogenesis of various inflammatory disorders, and the role of DNase enzyme with a focus on the possible function of nanotechnology in its management.
中性粒细胞是抵御病原体的主要宿主固有免疫细胞。中性粒细胞限制病原体传播的一种推测机制是中性粒细胞胞外诱捕网形成，其包括通过在质膜上形成孔隙将细胞核内容物释放到细胞质中。细胞脱氧核糖核酸（DNA）的挤出导致由与组蛋白和颗粒蛋白相关的核DNA组成的中性粒细胞胞外诱捕网（NETs）。中性粒细胞胞外诱捕网形成由酶肽基精氨酸脱亚氨酶4（PAD-4）驱动，该酶将精氨酸转化为瓜氨酸，导致染色质解聚、DNA分离并最终挤出。脱氧核糖核酸酶负责中性粒细胞胞外诱捕网的分解。一方面，脱氧核糖核酸酶的释放可能会干扰中性粒细胞胞外诱捕网的抗菌作用；此外，脱氧核糖核酸酶可保护组织免受脓毒症条件下中性粒细胞胞外诱捕网释放增加所导致的自我破坏。生理量的中性粒细胞胞外诱捕网有望在抗感染固有免疫反应中发挥作用。相反，体内异常高浓度的中性粒细胞胞外诱捕网若未被脱氧核糖核酸酶充分清除，则会损害组织并引发炎症。通过几种新方法，现在有可能避免中性粒细胞胞外诱捕网持续释放到细胞外环境中所造成的不利影响。在本综述中，我们重点介绍了中性粒细胞胞外诱捕网形成的基本机制、其在各种炎症性疾病发病机制中的意义以及脱氧核糖核酸酶的作用，特别关注了纳米技术在其管理中的可能作用。
