Understanding potential mechanisms of harm: the drivers of electronic cigarette-induced changes in alveolar macrophages, neutrophils and lung epithelial cells

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Colleges, School and Institutes


Electronic cigarettes are growing in popularity despite uncertainties regarding their long-term health implications. The link between cigarette smoking and initiation of chronic lung disease took decades to unpick so in vitro studies mimicking e-cigarette exposure aim to detect early indicators of harm. In response to e-cigarette exposure, alveolar macrophages adopt a pro-inflammatory phenotype of increased secretion of proinflammatory cytokines, reduction in phagocytosis and efferocytosis and reactive oxygen species generation. These effects are largely driven by free radical exposure, changes in PI3K/Akt signalling pathways, nicotine-induced reduction in phagocytosis receptors and impaired lipid homeostasis leading to a foam-like lipid laden phenotype. Neutrophils exhibit disrupted chemotaxis and transmigration to chemokines, reduced phagocytosis and bacterial killing and an increase in protease secretion without corresponding antiproteases in response to e-cigarette exposure. This is driven by an altered ability to respond and polarise towards chemoattractants, an activation of the p38 MAPK signalling pathway and inability to assemble NADPH oxidase. E-cigarettes induce lung epithelial cells to display decreased ciliary beat frequency and ion channel conductance ability as well as changes in chemokine secretion and surface protein expression. Changes in gene expression, mitochondrial function and signalling pathways have been demonstrated in lung epithelial cells to explain these changes. Many functional outputs of alveolar macrophages, neutrophils and lung epithelial cells have not yet been fully explored in the context of e-cigarette exposure, and the underlying driving mechanisms are poorly understood. This review discusses the current evidence surrounding the effects of e-cigarettes on alveolar macrophages, neutrophils and lung epithelial cells with particular focus on the cellular mechanisms of change.


Original languageEnglish
JournalAmerican journal of physiology. Lung cellular and molecular physiology
Early online date19 May 2021
Publication statusE-pub ahead of print - 19 May 2021


  • e-cigarettes, neutrophils, alveolar macrophages, lung epithelial cells, mechanisms