Cigarette smoke extract induces the release of extracellular vesicles by airway epithelial cells via cellular carbonyl stress

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Introduction: Secreted extracellular vesicles (EVs) participate in multiple processes by transferring proteins and RNA between cells. Yet, their contribution to chronic inflammation in the lungs is largely unexplored. We determined if exposure of airway epithelial cells (AEC) to cigarette smoke extract (CSE) results in release of pro-inflammatory EVs. Using the CSE components H2O2 and acrolein, we determined whether reactive oxygen species or thiol-reactive carbonyl compounds account for CSE-induced EV release.Methods: AEC were exposed for 24h to different concentrations of CSE, H2O2 or acrolein, in some experiments in the presence of the thiol-group bearing antioxidant N-acetylcysteine (NAC). Relative levels of CD63+CD81+ EVs in conditioned media were measured by bead-coupled flow cytometry. Oxidized and total GSH were assessed using a GSH reductase cycling assay.Results: CSE induced EV release in a concentration-dependent manner up to 2.3-fold at 1.5% CSE. This was paralleled by increases in cellular oxidized (3.1 fold) and total (5.8 fold) GSH. Incubation of CSE with GSH resulted in complete GSH oxidation, confirming direct thiol reactivity of CSE. NAC prevented CSE-induced EV-release, likely by scavenging thiol-reactive components of CSE. Similar to CSE, acrolein, but not H2O2, induced EV release in a NAC-reversible manner. Exposure of naïve macrophages to CSE-induced EVs resulted in increased release of TNFα.Conclusion: AEC release an increased quantity of EVs when exposed to CSE. This is likely mediated by reactive carbonyl compounds. These EVs exert pro-inflammatory effects that may contribute to the pathogenesis of COPD.
Original languageEnglish
Number of pages2
JournalEuropean Respiratory Journal
Issue numbersuppl 59
Publication statusPublished - 1 Sept 2015


  • COPD - mechanism
  • Cell biology
  • Smoking


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