Adverse impact of ambient PM2.5 on expression and trafficking of surfactant protein A through reactive oxygen species damage to lamellar bodies
Adverse impact of ambient PM2.5 on expression and trafficking of surfactant protein A through reactive oxygen species damage to lamellar bodies
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环境 PM2.5 通过活性氧损伤层状体对表面活性剂蛋白 A 的表达和运输产生不利影响
DOI：
10.1016/j.toxlet.2019.08.015
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发表时间：
2019-10-15
影响因子：
3.5
通讯作者：
Zhang, Xingliang
中科院分区：
文献类型：
--
作者：
Peng, Juanjuan;Zhang, Lingli;Zhang, Xingliang
直径小于2.5 μ m的颗粒物（PM2.5）容易沉积在肺泡上，降低人体健康。表面活性蛋白A（SurfactantProteinA，SP-A）是肺泡Ⅱ型上皮细胞板层体（LaminalBodies，LB）中最丰富的肺表面活性蛋白。PM2.5对SP-A的影响是多方面的，且难以解决，其潜在机制尚不清楚。本研究以Balb/c小鼠和A549细胞为研究对象，研究了PM2. 5对SP-A表达和分布的影响。结果表明，与对照组相比，低、中浓度PM2. 5逐渐增强SP-A蛋白和mRNA的表达，而高浓度PM2. 5显著降低SP-A蛋白，但对SP-A mRNA的表达无影响。随着PM2.5浓度的增加，SP-A向LB的运输逐渐受到干扰，同时负责SP-A蛋白运输和储存的LB的病变加重。活性氧的产生大量增加PM2.5暴露后，它被拮抗的氧化抑制剂N-乙酰半胱氨酸。随后，在暴露于高浓度PM2.5下，受损的LB和SP-A表达的下降得到了很好的挽救。本研究为研究PM2.5或柴油机尾气颗粒物对其他蛋白质运输和储存在LB中的不利影响提供了一个新的视角。
Particulate matter with a diameter of less than 2.5 mu m (PM2.5) easily deposits on lung alveoli and degrades human health. Surfactant protein A (SP-A) is the most abundant pulmonary surfactant protein stored in lamellar bodies (LBs) of alveolar epithelial type II cells. The impacts of PM2.5 on SP-A are multifaceted and intractable, and the underlying mechanism remains unclear. In this study, the expression and distribution of SP-A in Balb/c mice and A549 cells under PM2.5 exposure were investigated. The results showed that the low and medium concentration of PM2.5 gradually enhanced SP-A protein and mRNA expression, whereas the high concentration of PM2.5 conspicuously decreased SP-A protein but not its mRNA compared with the control. The trafficking of SP-A to LBs was gradually disturbed, and concomitantly, the lesions of LBs responsible for the transport and storage of SP-A protein were exacerbated with increased PM2.5 concentration. Reactive oxygen species production abundantly increased upon PM2.5 exposure, and it was antagonized by the oxidant inhibitor N-acetylcysteine. Subsequently, the injured LBs and the decrease in SP-A expression under exposure to the high concentration of PM2.5 were well rescued. The present study provides a new perspective to investigate the adverse effects of PM2.5 or diesel exhaust particles on other proteins transported to and stored in LBs.