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 8

ENDS exposure alters immune responses and recovery from influenza A infection.

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ENDS exposure alters immune responses and recovery from influenza A infe...
Eight-week-old mice were exposed to ENDS vapor or room air for 3 months. Subsequently, mice were infected with influenza A (45 TCID50/mouse or 20 TCID50/mouse). (A) Survival curve following infection with higher-titer viral infection — 45 TCID50/mouse. n = 8 per group. Significance was assessed by the log-rank (Mantel-Cox) test. *P < 0.05. (B) The weight loss and recovery curve following infection with influenza virus (20 TCID50/mouse) with quantification of weight loss on day 8 of infection. Significance was determined by Student’s t test. *P < 0.05; n = 10 per group. (C) Representative BAL cytospin preparations demonstrating the intracytoplasmic inclusions found in alveolar macrophages irrespective of infection status. Scale bars: 20 μm. (D) Histological analysis of lung tissue on day 14 following infection. Representative micrographs of H&E staining. Scale bars: 10 μm. (E) Objective quantification of pathological changes in lung H&E micrographs on day 14 following infection. n = 3 per group. (F) Cytokine concentrations for IFN-γ and TNF-α on day 14 following infection as determined by cytokine multiplex arrays. n = 5–9 per group. Significance was determined by Student’s t test. *P < 0.05. (G and H) Antibody titers for total (G) and hemagglutinin-specific IgG (H) from whole lung homogenate on day 14 following infection as determined by ELISA (n = 5–10 per group). Significance was determined by Student’s t test or 1-way ANOVA with Bonferroni’s correction for multiple comparisons. *P < 0.05. All data shown are representative of 3 or more independent experiments with n = 5–9 per group.