Neutrophil activation and NETosis are the predominant drivers of airway inflammation in an OVA/CFA/LPS induced murine model.
Neutrophil activation and NETosis are the predominant drivers of airway inflammation in an OVA/CFA/LPS induced murine model.
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中性粒细胞激活和 NETosis 是 OVA/CFA/LPS 诱导的小鼠模型中气道炎症的主要驱动因素
DOI：
10.1186/s12931-022-02209-0
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发表时间：
2022-10-21
影响因子：
5.8
通讯作者：
中科院分区：
文献类型：
--
作者：
研究背景哮喘是最常见的慢性疾病之一，全球有3亿多人患有哮喘。虽然大多数哮喘可以得到很好的控制，但患有严重哮喘的个体会经历反复发作，并对医疗保健系统造成巨大的经济负担。方法建立嗜中性粒细胞为主的过敏性哮喘小鼠模型，分析哮喘小鼠气道高反应性、气道炎症及肺组织病理改变。使用共聚焦显微镜和western blot.ResultsWe发现，卵清蛋白（OVA）/完全弗氏佐剂（CFA）/低剂量脂多糖（LPS）诱导的小鼠模型最好的概括了人类严重哮喘患者的气道复杂的改变。我们还观察到OVA/CFA/LPS暴露的小鼠在肺组织和骨髓中性粒细胞中产生大量的中性粒细胞胞外陷阱（NETs）。此外，我们发现，减少NET的生产或增加NET的降解可以减少气道炎症和气道高反应性。我们还确定了NET在嗜中性哮喘模型中发挥重要作用，并有助于嗜中性哮喘发病机制。NETs可能作为一个有希望的治疗嗜肺性哮喘的靶点。
BackgroundAsthma is one of the most common chronic diseases that affects more than 300 million people worldwide. Though most asthma can be well controlled, individuals with severe asthma experience recurrent exacerbations and impose a substantial economic burden on healthcare system. Neutrophil inflammation often occurs in patients with severe asthma who have poor response to glucocorticoids, increasing the difficulty of clinical treatment.MethodsWe established several neutrophil-dominated allergic asthma mouse models, and analyzed the airway hyperresponsiveness, airway inflammation and lung pathological changes. Neutrophil extracellular traps (NETs) formation was analyzed using confocal microscopy and western blot.ResultsWe found that the ovalbumin (OVA)/complete Freund’s adjuvant (CFA)/low-dose lipopolysaccharide (LPS)-induced mouse model best recapitulated the complex alterations in the airways of human severe asthmatic patients. We also observed OVA/CFA/LPS-exposed mice produced large quantities of neutrophil extracellular traps (NETs) in lung tissue and bone marrow neutrophils. Furthermore, we found that reducing the production of NETs or increasing the degradation of NETs can reduce airway inflammation and airway hyperresponsiveness.ConclusionOur findings identify a novel mouse model of neutrophilic asthma. We have also identified NETs play a significant role in neutrophilic asthma models and contribute to neutrophilic asthma pathogenesis. NETs may serve as a promising therapeutic target for neutrophilic asthma.
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DOI：
10.1164/rccm.201812-2351oc
发表时间：
2019-10-15
影响因子：
24.7
作者：
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