Neutrophil Extracellular Trap Formation Potential Correlates with Lung Disease Severity in COVID-19 Patients.

Neutrophil Extracellular Trap Formation Potential Correlates with Lung Disease Severity in COVID-19 Patients.
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DOI:
10.1007/s10753-021-01585-x
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发表时间:
2022-04
期刊:
影响因子:
5.1
通讯作者:
Moreland JG
Moreland JG
中科院分区:
医学2区
文献类型:
--
作者:
Kinnare N;Hook JS;Patel PA;Monson NL;Moreland JG

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严重的肺部炎症在危及生命的2019冠状病毒病(COVID-19)中很常见。本研究验证了以下假设:在严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)感染患者中,疾病进展过程早期的多形粒细胞(PMN,中性粒细胞)表型可预测肺部疾病严重程度峰值。越来越明显的是,PMN活化有助于由细胞外活性氧产生、颗粒胞吐伴随蛋白酶释放、中性粒细胞胞外陷阱(NET)形成和细胞因子释放引起的组织损伤。目前的研究集中在中性粒细胞激活响应SARS-CoV-2感染,特别是,NETs和肺部疾病之间的关联。这是一项在学术医学中心进行的前瞻性队列研究,患者在入院后4天内在3家三级医院入组:Clements University Hospital、帕克兰纪念医院和德克萨斯州达拉斯的儿童健康中心。根据峰值呼吸支持,将患者分为轻微或中度至重度肺部疾病。还招募了年龄、性别、人种和种族匹配的健康供体对照。与来自健康供体的中性粒细胞相比,来自COVID-19患者的中性粒细胞显示出更高的IL-8表达、弹性蛋白酶释放和NET形成。重要的是,来自COVID-19患者的中性粒细胞在没有任何额外刺激的情况下增强了NET形成,而在来自健康供体的PMN中未观察到。此外,PMA引起的循环PMN NET形成与肺部疾病的严重程度相关。我们推测中性粒细胞免疫表型可用于预测COVID-19患者的肺部疾病严重程度。在线版本包含补充材料,可通过10.1007/s10753-021-01585-x获得。
Severe lung inflammation is common in life-threatening coronavirus disease 2019 (COVID-19). This study tested the hypothesis that polymorphonuclear (PMN, neutrophil) phenotype early in the course of disease progression would predict peak lung disease severity in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is increasingly evident that PMN activation contributes to tissue injury resulting from extracellular reactive oxygen species generation, granule exocytosis with release of proteases, neutrophil extracellular trap (NET) formation, and release of cytokines. The current study focuses on PMN activation in response to SARS-CoV-2 infection, specifically, the association between NETs and lung disease. This is a prospective cohort study at an academic medical center with patients enrolled within 4 days of admission at 3 tertiary hospitals: Clements University Hospital, Parkland Memorial Hospital, and Children’s Health in Dallas, TX. Patients were categorized as having minimal or moderate to severe lung disease based on peak respiratory support. Healthy donor controls matched for age, sex, race, and ethnicity were also enrolled. Neutrophils from COVID-19 patients displayed greater IL-8 expression, elastase release, and NET formation as compared with neutrophils from healthy donors. Importantly, neutrophils from COVID-19 patients had enhanced NET formation in the absence of any additional stimulus, not seen in PMN from healthy donors. Moreover, PMA-elicited NET formation by circulating PMN correlated with severity of lung disease. We speculate that neutrophil immuno-phenotyping can be used to predict lung disease severity in COVID-19 patients. The online version contains supplementary material available at 10.1007/s10753-021-01585-x.
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