Electronic cigarettes disrupt lung lipid homeostasis and innate immunity independent of nicotine
Matthew C. Madison, … , David B. Corry, Farrah Kheradmand
Matthew C. Madison, … , David B. Corry, Farrah Kheradmand
Published October 1, 2019; First published September 4, 2019
Citation Information: J Clin Invest. 2019;129(10):4290-4304. https://doi.org/10.1172/JCI128531.
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Categories: Research Article Immunology Inflammation

Electronic cigarettes disrupt lung lipid homeostasis and innate immunity independent of nicotine

Abstract

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.

Authors

Matthew C. Madison, Cameron T. Landers, Bon-Hee Gu, Cheng-Yen Chang, Hui-Ying Tung, Ran You, Monica J. Hong, Nima Baghaei, Li-Zhen Song, Paul Porter, Nagireddy Putluri, Ramiro Salas, Brian E. Gilbert, Ilya Levental, Matthew J. Campen, David B. Corry, Farrah Kheradmand

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Figure 7

One-month exposure to ENDS vapor attenuates lung-resident macrophage function.

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One-month exposure to ENDS vapor attenuates lung-resident macrophage fun...
Lung-resident F4/80+ macrophages were isolated from whole lung tissue using magnetic beads following 1 month of exposure. Cells were cultured for 24 hours following isolation and supernatants and cells were harvested for the analyses. Individual data points represent technical replicates from pooled lungs of 4 mice per treatment group. (A) Absorbance values following the colorimetric, lactate dehydrogenase (LDH) cytotoxicity assay from 24-hour cultures of Air-, ENDS-vehicle–, and ENDS-nicotine–exposed groups. (B and C) Relative gene expression for Arg1 and Nos2 derived from RNA samples acquired from the cells after 24-hour culture. (D–F) Relative gene expression for (D) cytokines Tnfa and Il1b, (E) costimulatory molecules Cd86 and Cd80, and (F) viral recognition receptor Tlr7, derived from RNA samples in each treatment group acquired from the cells after 24-hour culture. (G) Relative gene expression for the transcription factor Irf7, a critical factor for type I IFN production, derived from RNA samples acquired from the cells in each treatment group after 24-hour culture. Cells were treated with either polyinosinic:polycytidylic acid (poly I:C) at a concentration of 10 μg/mL or PBS vehicle. All quantified results are expressed as means ± SEM. n = 4 or 5 per group. Significance was determined by 1-way ANOVA with Bonferroni’s correction for multiple comparisons. ****P < 0.0001, **P < 0.01, *P < 0.05. All data shown are representative of 3 or more independent 1-month experiments with n = 4 or 5 per group. NS, not significant; ND, none detected.