Association of COVID-19 inflammation with activation of the C5a-C5aR1 axis
Association of COVID-19 inflammation with activation of the C5a-C5aR1 axis
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DOI：
10.1038/s41586-020-2600-6
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发表时间：
2020-07-29
期刊：
影响因子：
64.8
通讯作者：
Vivier, Eric
中科院分区：
文献类型：
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作者：
Carvelli, Julien;Demaria, Olivier;Vivier, Eric
使用抗c5ar1单克隆抗体阻断C5a-C5aR1轴可预防与COVID-19相关的炎症。冠状病毒病2019 （COVID-19）是一种由感染严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）引起的疾病，已导致大流行(1)。C5a补体因子及其受体C5aR1（也称为CD88）通过招募和激活中性粒细胞和单核细胞，在几种炎症反应的启动和维持中发挥关键作用(1)。在这里，我们提供了免疫反应的纵向分析，包括免疫细胞的表型分析和评估在COVID-19严重程度的不同阶段患者的血液和支气管肺泡灌洗液中存在的可溶性因子，包括那些无症状或患有肺炎或急性呼吸窘迫综合征的患者。可溶性C5a水平与COVID-19严重程度成比例升高，血液和肺髓细胞中发现C5aR1受体高表达，支持C5a-C5aR1轴在急性呼吸窘迫综合征病理生理中的作用。抗C5aR1治疗性单克隆抗体可阻止c5a介导的人髓细胞募集和活化，抑制人C5aR1敲入小鼠的急性肺损伤。这些结果表明，阻断C5a-C5aR1轴可用于限制受损器官中髓样细胞的浸润，并防止与COVID-19患者急性呼吸窘迫综合征相关的过度肺部炎症和内皮炎。
Blockade of the C5a-C5aR1 axis using anti-C5aR1 monoclonal antibodies prevented inflammation associated with COVID-19.Coronavirus disease 2019 (COVID-19) is a disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has resulted in a pandemic(1). The C5a complement factor and its receptor C5aR1 (also known as CD88) have a key role in the initiation and maintenance of several inflammatory responses by recruiting and activating neutrophils and monocytes(1). Here we provide a longitudinal analysis of immune responses, including phenotypic analyses of immune cells and assessments of the soluble factors that are present in the blood and bronchoalveolar lavage fluid of patients at various stages of COVID-19 severity, including those who were paucisymptomatic or had pneumonia or acute respiratory distress syndrome. The levels of soluble C5a were increased in proportion to the severity of COVID-19 and high expression levels of C5aR1 receptors were found in blood and pulmonary myeloid cells, which supports a role for the C5a-C5aR1 axis in the pathophysiology of acute respiratory distress syndrome. Anti-C5aR1 therapeutic monoclonal antibodies prevented the C5a-mediated recruitment and activation of human myeloid cells, and inhibited acute lung injury in human C5aR1 knock-in mice. These results suggest that blockade of the C5a-C5aR1 axis could be used to limit the infiltration of myeloid cells in damaged organs and prevent the excessive lung inflammation and endothelialitis that are associated with acute respiratory distress syndrome in patients with COVID-19.