小柯机器人

研究发现COVID-19炎症与C5a–C5aR1信号轴激活的关联
2020-08-02 23:25
来源：小柯机器人

法国艾克斯-马赛大学Eric Vivier等研究人员揭示COVID-19炎症与C5a–C5aR1信号轴激活的关联。2020年7月29日，《自然》杂志在线发表了这项成果。

研究人员提供了对免疫应答的纵向分析，包括免疫细胞表型分析和对COVID-19严重程度不同阶段的患者血液和支气管肺泡灌洗液（BALF）中存在的可溶性因子的评估：严重症状、肺炎以及急性呼吸窘迫综合症（ARDS）。
 
研究人员发现，可溶性血C5a水平与血液和肺部骨髓细胞中的COVID-19严重性和高水平的C5aR1表达成比例，这支持ARDS的病理生理中C5a-C5aR1信号轴的作用。抗C5aR1治疗性单克隆抗体（mAb）阻止了C5aR1敲入小鼠中C5a介导的人类骨髓细胞招募和激活，并抑制了急性肺损伤（ALI）。
 
这些结果表明，C5a-C5aR1信号轴阻断可作为限制受损器官中髓样细胞浸润并预防COVID-19患者中与ARDS相关的过度肺部炎症和内皮炎症的方法。
 
据悉，冠状病毒病2019（COVID-19）是由严重急性呼吸系统综合症冠状病毒2（SARS-CoV-2）感染引起的新型大流行性疾病。C5a过敏毒素及其受体C5aR1（CD88）通过招募和激活肺中的中性粒细胞和单核细胞，在多种炎症反应的发生和维持中起关键作用。
 
附：英文原文

Title: Association of COVID-19 inflammation with activation of the C5a–C5aR1 axis

Author: Julien Carvelli, Olivier Demaria, Frdric Vly, Luciana Batista, Nassima Chouaki Benmansour, Joanna Fares, Sabrina Carpentier, Marie-Laure Thibult, Ariane Morel, Romain Remark, Pascale Andr, Agns Represa, Christelle Piperoglou, Pierre Yves Cordier, Erwan Le Dault, Christophe Guervilly, Pierre Simeone, Marc Gainnier, Yannis Morel, Mikael Ebbo, Nicolas Schleinitz, Eric Vivier

Issue&Volume: 2020-07-29

Abstract: Coronavirus disease 2019 (COVID-19) is a new pandemic disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1. The C5a anaphylatoxin and its receptor C5aR1 (CD88) play a key role in the initiation and maintenance of several inflammatory responses, by recruiting and activating neutrophils and monocytes in the lungs1. We provide a longitudinal analysis of immune responses, including immune cell phenotyping and assessments of the soluble factors present in the blood and broncho-alveolar lavage fluid (BALF) of patients at various stages of COVID-19 severity: paucisymptomatic, pneumonia and acute respiratory distress syndrome (ARDS). We report an increase in soluble C5a levels proportional to COVID-19 severity and high levels of C5aR1 expression in blood and pulmonary myeloid cells, supporting a role for the C5a-C5aR1 axis in the pathophysiology of ARDS. Anti-C5aR1 therapeutic monoclonal antibodies (mAbs) prevented C5a-mediated human myeloid cell recruitment and activation, and inhibited acute lung injury (ALI) in human C5aR1 knockin mice. These results suggest that C5a-C5aR1 axis blockade might be used as a means of limiting myeloid cell infiltration in damaged organs and preventing the excessive lung inflammation and endothelialitis associated with ARDS in COVID-19 patients.

DOI: 10.1038/s41586-020-2600-6

Source: https://www.nature.com/articles/s41586-020-2600-6

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html


本期文章：《自然》：Online/在线发表

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