Department of Internal Medicine, First Clinic of Internal Medicine, University of Genoa, Genoa, Italy.
Centre for Molecular Cardiology, University of Zürich, Schlieren, Switzerland.
Thromb Haemost. 2018 Jan;118(1):6-27. doi: 10.1160/TH17-09-0630. Epub 2018 Jan 5.
Neutrophil pathogen-killing mechanism termed neutrophil extracellular traps (NETs) has been recently identified. NETs consist of chromatin and histones along with serine proteases and myeloperoxidase and are induced by a great variety of infectious and non-infectious . NETosis is a kind of programmed neutrophil death characterized by chromatin decondensation and release of nuclear granular contents, mainly driven by peptidylarginine deiminase 4 citrullination of histones. Although classically related to the protection against infectious pathogens, nowadays NETs have been described as a player of several pathophysiological processes. Neutrophil dysregulation has been demonstrated in the pathogenesis of most representative vascular diseases, such as acute coronary syndrome, stroke and venous thrombosis. Indeed, NETs have been identified within atherosclerotic lesions and arterial thrombi in both human beings and animal models. Moreover, an imbalance in this mechanism has been proposed as a critical source of modified and/or externalized autoantigens in autoimmune and inflammatory diseases. Finally, an update on the role of NETs in the pathogenesis of cancer has been included. In the present review, based on papers released on PubMed and MEDLINE up to July 2017, we point to update the knowledge on NETs, from their structure to their roles in infectious diseases as well as in cardiovascular diseases, autoimmunity, metabolic disorders and cancer, with a look to future perspectives and therapeutic opportunities.
中性粒细胞的病原体杀伤机制被称为中性粒细胞胞外诱捕网（NETs），最近才被发现。NETs 由染色质和组蛋白以及丝氨酸蛋白酶和髓过氧化物酶组成，由各种感染性和非感染性因素诱导。NETosis 是一种程序化的中性粒细胞死亡，其特征是染色质解凝聚和核颗粒内容物的释放，主要由肽基精氨酸脱亚氨酶 4 对组蛋白的瓜氨酸化驱动。虽然经典上与对抗感染病原体有关，但现在已经描述了 NETs 在几种病理生理过程中的作用。中性粒细胞失调已在大多数代表性血管疾病（如急性冠状动脉综合征、中风和静脉血栓形成）的发病机制中得到证实。事实上，在人类和动物模型的动脉粥样硬化病变和动脉血栓中已经鉴定出 NETs。此外，该机制的失衡已被提出是自身免疫和炎症性疾病中修饰和/或外化自身抗原的关键来源。最后，还包括 NETs 在癌症发病机制中的作用的最新进展。在本综述中，基于截至 2017 年 7 月在 PubMed 和 MEDLINE 上发布的论文，我们指出了从 NETs 的结构到其在传染病以及心血管疾病、自身免疫、代谢紊乱和癌症中的作用的知识更新，展望未来的前景和治疗机会。
