Department of Biosciences, University of Salzburg, Hellbrunnerstrasse 34, 5020 Salzburg, Austria.
Institute of Pathology and Medical Genetics, University Hospital Basel, Schönbeinstrasse 40, 4031 Basel, Switzerland.
Dis Markers. 2021 Jul 30;2021:5566826. doi: 10.1155/2021/5566826. eCollection 2021.
An excess formation of neutrophil extracellular traps (NETs), previously shown to be strongly associated with cytokine storm and acute respiratory distress syndrome (ARDS) with prevalent endothelial dysfunction and thrombosis, has been postulated to be a central factor influencing the pathophysiology and clinical presentation of severe COVID-19. A growing number of serological and morphological evidence has added to this assumption, also in regard to potential treatment options. In this study, we used immunohistochemistry and histochemistry to trace NETs and their molecular markers in autopsy lung tissue from seven COVID-19 patients. Quantification of key immunomorphological features enabled comparison with non-COVID-19 diffuse alveolar damage. Our results strengthen and extend recent findings, confirming that NETs are abundantly present in seriously damaged COVID-19 lung tissue, especially in association with microthrombi of the alveolar capillaries. In addition, we provide evidence that low-density neutrophils (LDNs), which are especially prone to NETosis, contribute substantially to COVID-19-associated lung damage in general and vascular blockages in particular.
中性粒细胞胞外诱捕网（NETs）的过度形成，先前被强烈认为与细胞因子风暴和急性呼吸窘迫综合征（ARDS）有关，其特征为普遍存在的内皮功能障碍和血栓形成，被认为是影响严重 COVID-19 病理生理学和临床表现的核心因素。越来越多的血清学和形态学证据对此假设进行了补充，也涉及到潜在的治疗选择。在这项研究中，我们使用免疫组织化学和组织化学方法在来自 7 名 COVID-19 患者的尸检肺组织中追踪 NETs 及其分子标志物。关键免疫形态学特征的定量分析使我们能够与非 COVID-19 弥漫性肺泡损伤进行比较。我们的研究结果证实并扩展了最近的发现，即 NETs 在严重受损的 COVID-19 肺组织中大量存在，尤其是与肺泡毛细血管微血栓有关。此外，我们还提供了证据表明，易发生 NETosis 的低密度中性粒细胞（LDNs）通常会导致 COVID-19 相关的肺部损伤，尤其是血管阻塞。
