在SARS-CoV-2感染期间,慢性酒精使用会使支气管细胞产生改变的炎症反应和屏障功能障碍
Kristen F Easley1, R Clayton Edenfield2,3, Megan E J Lott2
1Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Emory University School of Medicine, Atlanta, Georgia, United States.
概括
酒精使用障碍 (AUD) 通过损害呼吸道上皮质屏障功能和加剧炎症反应,增加COVID-19的严重程度. 在SARS-CoV-2感染后,AUD对细胞产生更大的炎症和功能障碍,这表明AUD是一个重要的风险因素.
科学领域:
- 肺部医学 肺部医学
- 传染性疾病 传染性疾病
- 细胞生物学 细胞生物学
背景情况:
- 酒精使用障碍 (AUD) 与严重急性呼吸困扰综合征 (ARDS) 和呼吸道感染的较差结果有关.
- 了解AUD对SARS-CoV-2感染的影响对于公共卫生至关重要.
- 在AUD患者中,对SARS-CoV-2感染的早期细胞反应需要进一步调查.
研究的目的:
- 调查AUD是否是SARS-CoV-2感染严重后果的风险因素.
- 检查SARS-CoV-2暴露后AUD和没有AUD的个体的支气管上皮细胞中的早期细胞反应.
- 确定AUD对气道上皮质屏障功能和对SARS-CoV-2的炎症反应的影响.
主要方法:
- 从AUD和非AUD个体培养的分化支气管上皮细胞被SARS-CoV-2感染.
- RNA测序 (RNA-seq) 分析了未感染细胞中的基因表达.
- 通过脑膜电阻测量了屏障功能;多重分析量化了细胞因子分泌.
主要成果:
- 感染后72小时,AUD细胞表现出丰富的表皮基因表达和显著下降的屏障功能.
- 在AUD细胞中,SARS-CoV-2感染破坏了紧密结节的组织 (ZO-1的claudin-7错位).
- 与非AUD细胞相比,AUD细胞表现出增强的促炎细胞因子 (TNFα,IL-1β,IFNγ) 和降低的屏障保护细胞因子 (EGF,GM-CSF) 的分泌.
结论:
- AUD启动气道上皮细胞,导致SARS-CoV-2感染时炎症增加和屏障功能障碍.
- 这些发现支持AUD作为更严重的COVID-19结果的风险因素.
- AUD诱导了一种与对SARS-CoV-2的敏感性和反应相关的细胞表型.
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