带有蛋白质的致病性细胞外囊泡与吸烟和慢性阻塞性肺部疾病有关
Matthew C Madison1, Camilla Margaroli2, Kristopher R Genschmer3,4
1Department of Clinical and Diagnostic Science.
American journal of respiratory and critical care medicine
|September 15, 2023
概括
香烟烟雾产生细胞外囊泡 (EVs) 与中性粒细胞弹性酶和矩阵金属蛋白酶12. 这些EV会导致肺损伤和肺气,为慢性阻塞性肺病研究提供了一个新模式.
科学领域:
- 肺部医学 肺部医学
- 细胞外囊泡生物学 细胞外囊泡生物学
- 蛋白质酶生物化学 蛋白质酶生物化学
背景情况:
- 细胞外囊泡 (EVs) 越来越多地与慢性阻塞性肺病 (COPD) 等肺部疾病有关.
- 香烟烟雾 (CS) 是COPD的主要风险因素,但其与疾病驱动电动汽车的直接联系尚不清楚.
研究的目的:
- 调查CS暴露是否会诱导蛋白质溶解性EV特征,从而导致COPD的发病.
- 确定与CS暴露相关的EV上的特定蛋白酶及其在肺损伤中的作用.
主要方法:
- 分析了暴露于烟雾的小鼠和人类吸烟者的EV中的蛋白酶表达和活性.
- 这些EV的致病性通过转移到天真的接受者小鼠进行评估,然后进行病理评分.
- 根据其细胞起源和表面蛋白酶含量来表征EV.
主要成果:
- 鉴定出一种独特的EV概况,其特点是来自中性粒细胞和巨细胞的EVs.
- 这些EV显示了中性粒细胞弹性酶 (NE) 和矩阵金属蛋白酶12 (MMP12) 的高表面表达.
- 来自小鼠和人类的CS诱导的EV在接受者小鼠中引起了快速的肺损伤,NE和MMP12具有附加效应.
结论:
- 暴露于CS驱动了含有NE和MMP12的EVs的产生,这些足以引起肺气性疾病.
- 这些EV可以作为COPD发展的预后指标.
- 该研究建立了使用CS诱导的EV进行COPD研究的新型临床前模型,并揭示了CS诱导的保护机制.
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