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 September 4, 2019
Citation Information: J Clin Invest. 2019;129(10):4290-4304. https://doi.org/10.1172/JCI128531.
View: Text | PDF
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

×

Figure 3

TEM imaging of lipid inclusions in alveolar macrophage and alveolar type II pneumocytes.

Options: View larger image (or click on image) Download as PowerPoint
TEM imaging of lipid inclusions in alveolar macrophage and alveolar type...
Following 4 months of exposure, lungs from Air, ENDS-vehicle, and ENDS-nicotine groups were fixed and processed for electron microscopic analysis. (A) Representative micrographs of alveolar macrophages demonstrating lipid inclusions and increased presence of lysosomal compartments in ENDS-vehicle and ENDS-nicotine groups (white arrows). Scale bars: 2000 nm. 80 kV high voltage. (B) Higher magnification of the lipid inclusions (right) and lysosomes (left) observed in ENDS-vehicle and ENDS-nicotine groups. Scale bars: 200 nm. 80 kV high voltage. (C) Representative micrographs of alveolar type II pneumocytes (ATIIs) demonstrating normal, uniform lamellar bodies in AIR-exposed mice (red arrow) and atypical lamellar body structures in ENDS-vehicle and ENDS-nicotine groups (white arrows). Scale bars: 2000 nm. 80 kV high voltage. (D) Higher magnification of the representative lamellar bodies observed in AIR, ENDS-vehicle, and ENDS-nicotine groups. Scale bars: 500 nm. 80 kV high voltage. (E) Blinded quantification of atypical lamellar bodies observed within ATIIs. The quantified results are expressed as the percentage of atypical lamellar bodies per total lamellar body count in each cell (mean ± SEM). n = 5 or 6 per group. Each data point represents a single ATII, all of which were located and imaged by scanning 3 or more independent mounted grids per experimental group. Significance was determined by Student’s t test. *P < 0.05.