Abstract
Objective: Vaping may increase the cytotoxic effects of e-cigarette liquid (ECL). We compared the effect of unvaped ECL to e-cigarette vapour condensate (ECVC) upon alveolar macrophage (AM) function.
Methods: AMs 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 was assessed.
Results: Macrophage culture with ECL or ECVC resulted in 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 1 isoform PI3 kinase inhibitors partially inhibited the effects of ECVC/nfECVC upon macrophage viability and apoptosis. Secretion of IL-6, TNF-α, CXCL-8, MCP-1 and MMP-9 were 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.
Conclusions: ECVC 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’s is partly dependent on nicotine. Inhibition of phagocytosis also suggests users may suffer from impaired bacterial clearance. Whilst 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.
Methods: AMs 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 was assessed.
Results: Macrophage culture with ECL or ECVC resulted in 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 1 isoform PI3 kinase inhibitors partially inhibited the effects of ECVC/nfECVC upon macrophage viability and apoptosis. Secretion of IL-6, TNF-α, CXCL-8, MCP-1 and MMP-9 were 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.
Conclusions: ECVC 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’s is partly dependent on nicotine. Inhibition of phagocytosis also suggests users may suffer from impaired bacterial clearance. Whilst 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.
| Original language | English |
|---|---|
| Pages (from-to) | 1161-1169 |
| Number of pages | 9 |
| Journal | Thorax |
| Volume | 73 |
| Issue number | 12 |
| Early online date | 13 Aug 2018 |
| DOIs | |
| Publication status | Published - Dec 2018 |
Keywords
- smoking
- nicotine
- vaping
- inflammation
- phagocytosis
- macrophage
- P13 kinase