Proteome Profiling of Recombinant DNase Therapy in Reducing NETs and Aiding Recovery in COVID-19 Patients.
Proteome Profiling of Recombinant DNase Therapy in Reducing NETs and Aiding Recovery in COVID-19 Patients.
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DOI：
10.1016/j.mcpro.2021.100113
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Linder A
中科院分区：
文献类型：
--
作者：
Fisher J;Mohanty T;Karlsson CAQ;Khademi SMH;Malmström E;Frigyesi A;Nordenfelt P;Malmstrom J;Linder A
严重的 2019 年冠状病毒病 (COVID-19) 可导致肺炎和急性呼吸衰竭。呼吸道粘液积聚是该疾病的标志，可导致低氧血症。在这里，我们表明，对 COVID-19 重症患者痰液的定量蛋白质组分析显示，中性粒细胞胞外陷阱 (NET) 成分含量较高，这一点已通过显微镜证实。过量 NET 形成的细胞外 DNA 会增加痰液粘度并导致急性呼吸窘迫综合征。重组人 DNase（Pulmozyme；Roche）已被证明有助于降低痰液粘度并改善肺功能。我们使用临床批准的雾化 Pulmozyme 治疗了 5 名患有急性症状的 COVID-19 患者。该药物没有出现任何不良反应，治疗后所有重症 COVID-19 患者的氧饱和度和恢复情况均得到改善。治疗后痰液和血浆样本的免疫荧光和蛋白质组分析显示，NETs 显着减少，并且出现一系列统计学上显着的蛋白质组变化，表明出血、血浆渗漏和气道炎症减少，患者血浆中的全身炎症状态减少。总而言之，结果表明 NET 会导致 COVID-19 的急性呼吸衰竭，而降解 NET 可能会减少患者对外部高流量氧疗的依赖。使用重组人 DNase 靶向 NET 可能对 COVID-19 疾病具有显着的治疗意义，值得进一步研究。重症 COVID-19 患者痰液中中性粒细胞胞外陷阱 (NET) 含量较高。重组人 DNase 减少了痰中的 NET。 NET 减少与恢复和氧合改善相关。血浆和痰液的质谱分析表明炎症已消退。中性粒细胞通过形成中性粒细胞胞外陷阱 (NET) 来促进细胞外 DNA 库，从而导致痰液粘稠、肺部炎症和感染期间气体交换受阻。在这里，我们使用质谱和免疫荧光分析证明了重症 COVID-19 患者的痰液中存在 NET。使用临床批准的重组人 DNA 酶治疗可减少 NET，并与改善恢复和减少炎症相关。使用 DNase 靶向 NET 可能对 COVID-19 疾病具有显着的治疗意义，值得进一步研究。
Severe coronavirus disease 2019 (COVID-19) can result in pneumonia and acute respiratory failure. Accumulation of mucus in the airways is a hallmark of the disease and can result in hypoxemia. Here, we show that quantitative proteome analysis of the sputum from severe patients with COVID-19 reveal high levels of neutrophil extracellular trap (NET) components, which was confirmed by microscopy. Extracellular DNA from excessive NET formation can increase sputum viscosity and lead to acute respiratory distress syndrome. Recombinant human DNase (Pulmozyme; Roche) has been shown to be beneficial in reducing sputum viscosity and improve lung function. We treated five patients pwith COVID-19 resenting acute symptoms with clinically approved aerosolized Pulmozyme. No adverse reactions to the drug were seen, and improved oxygen saturation and recovery in all severely ill patients with COVID-19 was observed after therapy. Immunofluorescence and proteome analysis of sputum and blood plasma samples after treatment revealed a marked reduction of NETs and a set of statistically significant proteome changes that indicate reduction of hemorrhage, plasma leakage and inflammation in the airways, and reduced systemic inflammatory state in the blood plasma of patients. Taken together, the results indicate that NETs contribute to acute respiratory failure in COVID-19 and that degrading NETs may reduce dependency on external high-flow oxygen therapy in patients. Targeting NETs using recombinant human DNase may have significant therapeutic implications in COVID-19 disease and warrants further studies. High levels of neutrophil extracellular traps (NETs) in the sputum of severe COVID-19 patients. Recombinant human DNase decreased NETs in sputum. Reduced NETs were associated with recovery and improved oxygenation. Mass spectrometry analyses of plasma and sputum indicate resolution of inflammation. Neutrophils contribute to the extracellular DNA pool by forming neutrophil extracellular traps (NETs), which cause sputum thickening, pulmonary inflammation, and hindrance to gaseous exchange during infections. Here, we demonstrate the presence of NETs in sputum from severe COVID-19 patients using mass spectrometry and immunofluorescence analyses. Treatment with clinically approved recombinant human DNase reduced NETs and was associated with improved recovery and reduced inflammation. Targeting NETs using DNase may have significant therapeutic implications in COVID-19 disease and warrants further studies.
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影响因子：
3.7
作者：
Hemmers S;Teijaro JR;Arandjelovic S;Mowen KA
通讯作者：
Mowen KA
DOI：
10.1056/nejmra0910061
发表时间：
2010-12-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
Fahy JV;Dickey BF
通讯作者：
Dickey BF
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
4.5
作者：
de la Rica, Roberto;Borges, Marcio;Gonzalez-Freire, Marta
通讯作者：
Gonzalez-Freire, Marta
影响因子：
168.9
作者：
Huang, Chaolin;Wang, Yeming;Cao, Bin
通讯作者：
Cao, Bin