Electronic cigarettes disrupt lung lipid homeostasis and innate immunity independent of nicotine
Electronic cigarettes disrupt lung lipid homeostasis and innate immunity independent of nicotine
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DOI：
10.1172/jci128531
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发表时间：
2019-10-01
影响因子：
15.9
通讯作者：
Kheradmand, Farrah
中科院分区：
文献类型：
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作者：
Madison, Matthew C.;Landers, Cameron T.;Kheradmand, Farrah
电子尼古丁输送系统（ENDS）或电子烟已成为青少年和成年人中流行的娱乐工具。虽然使用ENDS通常被宣传为传统香烟的更安全的替代品，但很少有全面的研究评估汽化尼古丁及其相关溶剂丙二醇（PG）和植物甘油（VG）的长期影响。在这里，我们表明，与烟雾暴露相比，接受ENDS蒸汽4个月的小鼠没有发生肺部炎症或肺气肿。然而，ENDS暴露，独立于尼古丁，改变肺泡巨噬细胞和上皮细胞中的肺脂质稳态。肺的全面脂质组学和结构分析显示肺泡巨噬细胞中的异常磷脂和气道中的表面活性剂相关磷脂增加。除了ENDS诱导的脂质沉积外，慢性ENDS蒸汽暴露下调了居民巨噬细胞对病毒病原体的先天免疫。此外，与尼古丁无关，感染流感的ENDS暴露小鼠表现出增强的肺部炎症和组织损伤。总之，我们的研究结果表明，慢性电子烟蒸汽异常地改变了肺上皮细胞和常驻免疫细胞的生理学，并促进了对感染性挑战的不良反应。值得注意的是，脂质体内平衡和免疫损伤的改变与尼古丁无关，因此需要对电子烟中使用的溶剂进行更广泛的研究。
Electronic nicotine delivery systems (ENDS) or e-cigarettes have emerged as a popular recreational tool among adolescents and adults. Although the use of ENDS is often promoted as a safer alternative to conventional cigarettes, few comprehensive studies have assessed the long-term effects of vaporized nicotine and its associated solvents, propylene glycol (PG) and vegetable glycerin (VG). Here, we show that compared with smoke exposure, mice receiving ENDS vapor for 4 months failed to develop pulmonary inflammation or emphysema. However, ENDS exposure, independent of nicotine, altered lung lipid homeostasis in alveolar macrophages and epithelial cells. Comprehensive lipidomic and structural analyses of the lungs revealed aberrant phospholipids in alveolar macrophages and increased surfactant-associated phospholipids in the airway. In addition to ENDS-induced lipid deposition, chronic ENDS vapor exposure downregulated innate immunity against viral pathogens in resident macrophages. Moreover, independent of nicotine, ENDS-exposed mice infected with influenza demonstrated enhanced lung inflammation and tissue damage. Together, our findings reveal that chronic e-cigarette vapor aberrantly alters the physiology of lung epithelial cells and resident immune cells and promotes poor response to infectious challenge. Notably, alterations in lipid homeostasis and immune impairment are independent of nicotine, thereby warranting more extensive investigations of the vehicle solvents used in e-cigarettes.