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中性粒细胞的“解除武装”机制
作者:小柯机器人 发布时间:2020/1/15 11:30:07

西班牙马德里国立心血管病研究中心Andrés Hidalgo研究团队,发现中性粒细胞蛋白质组程序性“解除武装”机制如何减弱炎症的程度。相关论文2020年1月13日在线发表在国际学术期刊《自然—免疫学》上。

研究人员发现了一种细胞内在机制,其可以修饰处于循环中的中性粒细胞蛋白质组,并导致颗粒含量的逐渐降低和中性粒细胞胞外诱捕网(NETs)形成能力下降。这种机制是由受体CXCR2和昼夜节律调控。因此,在一天中的某个时间或颗粒含量较低的小鼠突变体中,该机制可以保护肺免受炎性损伤。蛋白质组、颗粒含量和NET形成的改变也发生在人类嗜中性粒细胞中,并且与肺炎患者呼吸窘迫的发生率和严重程度相关。该发现揭示了嗜中性粒细胞的“解除武装”机制,以及该机制如何通过耗尽存储的蛋白质以减少炎症程度。

据了解,中性粒细胞的抗菌功能可通过颗粒中存储的防御性蛋白质库以及形成中性粒细胞胞外诱捕网(NETs)来完成。然而,这些结构自身的毒性威胁着高度血管化的组织,如肺。

附:英文原文

Title: Programmed ‘disarming’ of the neutrophil proteome reduces the magnitude of inflammation

Author: Jose M. Adrover, Alejandra Aroca-Crevilln, Georgiana Crainiciuc, Fernando Ostos, Yeny Rojas-Vega, Andrea Rubio-Ponce, Catia Cilloniz, Elena Bonzn-Kulichenko, Enrique Calvo, Daniel Rico, Mara A. Moro, Christian Weber, Ignacio Lizasoan, Antoni Torres, Jess Ruiz-Cabello, Jess Vzquez, Andrs Hidalgo

Issue&Volume: 2020-01-13

Abstract: The antimicrobial functions of neutrophils are facilitated by a defensive armamentarium of proteins stored in granules, and by the formation of neutrophil extracellular traps (NETs). However, the toxic nature of these structures poses a threat to highly vascularized tissues, such as the lungs. Here, we identified a cell-intrinsic program that modified the neutrophil proteome in the circulation and caused the progressive loss of granule content and reduction of the NET-forming capacity. This program was driven by the receptor CXCR2 and by regulators of circadian cycles. As a consequence, lungs were protected from inflammatory injury at times of day or in mouse mutants in which granule content was low. Changes in the proteome, granule content and NET formation also occurred in human neutrophils, and correlated with the incidence and severity of respiratory distress in pneumonia patients. Our findings unveil a ‘disarming’ strategy of neutrophils that depletes protein stores to reduce the magnitude of inflammation.

DOI: 10.1038/s41590-019-0571-2

Source: https://www.nature.com/articles/s41590-019-0571-2

期刊信息

Nature Immunology:《自然—免疫学》,创刊于2000年。隶属于施普林格·自然出版集团,最新IF:23.53
官方网址:https://www.nature.com/ni/
投稿链接:https://mts-ni.nature.com/cgi-bin/main.plex