Pro-inflammatory effects of e-cigarette vapour condensate on human alveolar macrophages

• Published in: Thorax Vol. 73; no. 12; pp. 1161 - 1169
• Main Authors: Scott, Aaron, Lugg, Sebastian T, Aldridge, Kerrie, Lewis, Keir E, Bowden, Allen, Mahida, Rahul Y, Grudzinska, Frances Susanna, Dosanjh, Davinder, Parekh, Dhruv, Foronjy, Robert, Sapey, Elizabeth, Naidu, Babu, Thickett, David R
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group LTD 01.12.2018; BMJ Publishing Group
• Series: Original article
• Subjects: Acetylcysteine - pharmacology; Antioxidants - pharmacology; Apoptosis; Apoptosis - drug effects; Cell Survival - drug effects; Chemokine CCL2 - metabolism; Chromatography; Chronic obstructive pulmonary disease; Complex Mixtures - adverse effects; Cytotoxicity; Electronic cigarettes; Electronic Nicotine Delivery Systems; Gases - adverse effects; Health hazards; Humans; Inflammation; Inflammation - etiology; Inflammation - metabolism; Interleukin-6 - metabolism; Interleukin-8 - metabolism; Macrophages, Alveolar - pathology; Macrophages, Alveolar - physiology; Matrix Metalloproteinase 9 - metabolism; Methods; Necrosis - etiology; Nicotine; Nicotine - adverse effects; Oxidative stress; Phagocytosis - drug effects; Phosphoinositide-3 Kinase Inhibitors; Physiology; Protein Kinase Inhibitors - pharmacology; Reactive Oxygen Species - metabolism; Research parks; Smoking; THP-1 Cells; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Vaping - adverse effects; United Kingdom > UK; United States > US; macrophage biology; oxidative stress; respiratory infection
• ISSN: 0040-6376; 1468-3296
• DOI: 10.1136/thoraxjnl-2018-211663

ObjectiveVaping may increase the cytotoxic effects of e-cigarette liquid (ECL). We compared the effect of unvaped ECL to e-cigarette vapour condensate (ECVC) on alveolar macrophage (AM) function.MethodsAMs were treated with ECVC and nicotine-free ECVC (nfECVC). AM viability, apoptosis, necrosis, cytokine, chemokine and protease release, reactive oxygen species (ROS) release and bacterial phagocytosis were assessed.ResultsMacrophage culture with ECL or ECVC resulted in a dose-dependent reduction in cell viability. ECVC was cytotoxic at lower concentrations than ECL and resulted in increased apoptosis and necrosis. nfECVC resulted in less cytotoxicity and apoptosis. Exposure of AMs to a sub-lethal 0.5% ECVC/nfECVC increased ROS production approximately 50-fold and significantly inhibited phagocytosis. Pan and class one isoform phosphoinositide 3 kinase inhibitors partially inhibited the effects of ECVC/nfECVC on macrophage viability and apoptosis. Secretion of interleukin 6, tumour necrosis factor α, CXCL-8, monocyte chemoattractant protein 1 and matrix metalloproteinase 9 was significantly increased following ECVC challenge. Treatment with the anti-oxidant N-acetyl-cysteine (NAC) ameliorated the cytotoxic effects of ECVC/nfECVC to levels not significantly different from baseline and restored phagocytic function.ConclusionsECVC is significantly more toxic to AMs than non-vaped ECL. Excessive production of ROS, inflammatory cytokines and chemokines induced by e-cigarette vapour may induce an inflammatory state in AMs within the lung that is partly dependent on nicotine. Inhibition of phagocytosis also suggests users may suffer from impaired bacterial clearance. While further research is needed to fully understand the effects of e-cigarette exposure in humans in vivo, we caution against the widely held opinion that e-cigarettes are safe.