Delayed neutrophil apoptosis may enhance NET formation in ARDS.
Delayed neutrophil apoptosis may enhance NET formation in ARDS.
复制标题
延迟性中性粒细胞凋亡可能促进ARDS网状结构的形成。
DOI：
10.1186/s12931-022-02065-y
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发表时间：
2022-06-13
影响因子：
5.8
通讯作者：
中科院分区：
文献类型：
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作者：
急性呼吸窘迫综合征（ARDS）是一种中性粒细胞相关疾病。 ARDS 中已描述了中性粒细胞凋亡延迟和中性粒细胞胞外陷阱 (NET) 水平增加。我们的目的是研究这些现象与其作为炎症驱动因素的潜力之间的关系。我们假设中性粒细胞凋亡延迟可能会增强 ARDS 中 NET 的形成。我们的研究主要从三个方面进行：临床研究、动物实验、体外实验。首先，我们比较健康对照和ARDS患者中性粒细胞凋亡和NET水平的差异，分析ARDS中中性粒细胞凋亡和NET水平的相关性。然后，我们进行了动物实验来验证中性粒细胞凋亡对脂多糖诱导的急性肺损伤（LPS-ALI）小鼠中NET形成的影响。此外，本研究在细胞水平探讨了中性粒细胞凋亡与NETs之间的关系。使用形态学分析、流式细胞术和蛋白质印迹评估细胞凋亡。使用免疫荧光、PicoGreen 测定、SYTOX Green 染色和蛋白质印迹法测定 NET 形成。 ARDS 中性粒细胞由于细胞凋亡延迟而寿命更长，而细胞周期蛋白依赖性激酶抑制剂 AT7519 逆转了 ARDS 中性粒细胞和 LPS-ALI 小鼠支气管肺泡灌洗液 (BALF) 中的中性粒细胞的这一现象。含有促生存因子（LPS 或 GM-CSF）的培养基中的中性粒细胞会形成更多的 NET，这也可以被 AT7519 逆转。通过促进中性粒细胞凋亡可以减少组织损伤。 ARDS 中寿命延长的中性粒细胞通常会增强 NET 的形成，从而加剧炎症。增强 ARDS 中的中性粒细胞凋亡可以减少 NET 的形成，抑制炎症，从而缓解 ARDS。在线版本包含可在 10.1186/s12931-022-02065-y 获取的补充材料。
Acute respiratory distress syndrome (ARDS) is a neutrophil-associated disease. Delayed neutrophil apoptosis and increased levels of neutrophil extracellular traps (NETs) have been described in ARDS. We aimed to investigate the relationship between these phenomena and their potential as inflammation drivers. We hypothesized that delayed neutrophil apoptosis might enhance NET formation in ARDS. Our research was carried out in three aspects: clinical research, animal experiments, and in vitro experiments. First, we compared the difference between neutrophil apoptosis and NET levels in healthy controls and patients with ARDS and analyzed the correlation between neutrophil apoptosis and NET levels in ARDS. Then, we conducted animal experiments to verify the effect of neutrophil apoptosis on NET formation in Lipopolysaccharide-induced acute lung injury (LPS-ALI) mice. Furthermore, this study explored the relationship between neutrophil apoptosis and NETs at the cellular level. Apoptosis was assessed using morphological analysis, flow cytometry, and western blotting. NET formation was determined using immunofluorescence, PicoGreen assay, SYTOX Green staining, and western blotting. ARDS neutrophils lived longer because of delayed apoptosis, and the cyclin-dependent kinase inhibitor, AT7519, reversed this phenomenon both in ARDS neutrophils and neutrophils in bronchoalveolar lavage fluid (BALF) of LPS-ALI mice. Neutrophils in a medium containing pro-survival factors (LPS or GM-CSF) form more NETs, which can also be reversed by AT7519. Tissue damage can be reduced by promoting neutrophil apoptosis. Neutrophils with extended lifespan in ARDS usually enhance NET formation, which aggravates inflammation. Enhancing neutrophil apoptosis in ARDS can reduce the formation of NETs, inhibit inflammation, and consequently alleviate ARDS. The online version contains supplementary material available at 10.1186/s12931-022-02065-y.
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DOI：
10.1001/jama.2016.6338
发表时间：
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期刊：
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影响因子：
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作者：
Altznauer, F;Martinelli, S;Yousefi, S;Thürig, C;Schmid, I;Conway, EM;Schöni, MH;Vogt, P;Mueller, C;Fey, MF;Zangemeister-Wittke, U;Simon, HU
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