Vascular occlusion by neutrophil extracellular traps in COVID-19
Vascular occlusion by neutrophil extracellular traps in COVID-19
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DOI：
10.1016/j.ebiom.2020.102925
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发表时间：
2020-08-01
期刊：
影响因子：
11.1
通讯作者：
Herrmann, Martin
中科院分区：
文献类型：
--
作者：
Leppkes, Moritz;Knopl, Jasmin;Herrmann, Martin
背景：2019 年冠状病毒引起的疾病 (COVID-19) 可能会因严重的器官损伤而变得复杂，导致肺部和其他器官功能障碍。 COVID-19 引发器官损伤的过程尚不完全清楚。方法：样本来自住院患者捐赠。采用流式细胞术、酶联免疫吸附测定和免疫组织化学检查血清、血浆和尸检来源的组织切片。 患者发现：在这里，我们表明，严重的 COVID-19 的特点是微血管内高度明显地形成中性粒细胞胞外陷阱 (NET)。 NETs 的血管内聚集会导致受影响血管快速闭塞、微循环紊乱和器官损伤。在严重的 COVID-19 中，中性粒细胞被强烈激活并采取所谓的低密度表型，易于自发形成 NET。因此，表明 NET 周转率的标记物在 COVID-19 中持续增加，并且与疾病严重程度相关。 COVID-19患者的肺部和其他器官的组织病理学显示，与内皮损伤相关的聚集的NET导致大量微血管充血。解释：这些数据表明，严重的COVID-19中的器官功能障碍与过度的NET形成和血管损伤有关。 (c) 2020 作者。由 Elsevier B.V. 出版。这是一篇遵循 CC BY-NC-ND 许可的开放获取文章。 (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Background: Coronavirus induced disease 2019 (COVID-19) can be complicated by severe organ damage leading to dysfunction of the lungs and other organs. The processes that trigger organ damage in COVID-19 are incompletely understood.Methods: Samples were donated from hospitalized patients. Sera, plasma, and autopsy-derived tissue sections were examined employing flow cytometry, enzyme-linked immunosorbent assays, and immunohistochemistry.Patient findings: Here, we show that severe COVID-19 is characterized by a highly pronounced formation of neutrophil extracellular traps (NETs) inside the micro-vessels. Intravascular aggregation of NETs leads to rapid occlusion of the affected vessels, disturbed microcirculation, and organ damage. In severe COVID-19, neutrophil granulocytes are strongly activated and adopt a so-called low-density phenotype, prone to spontaneously form NETs. In accordance, markers indicating NET turnover are consistently increased in COVID-19 and linked to disease severity. Histopathology of the lungs and other organs from COVID-19 patients showed congestions of numerous micro-vessels by aggregated NETs associated with endothelial damage.Interpretation: These data suggest that organ dysfunction in severe COVID-19 is associated with excessive NET formation and vascular damage. (c) 2020 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license. (http://creativecommons.org/licenses/by-nc-nd/4.0/)