Electronic cigarette inhalation alters innate immunity and airway [PDF]

Abstract. Electronic (e)-cigarette use is rapidly rising, with 20 % of Americans ages 25–44 now using these drug deliv

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Electronic cigarette inhalation alters innate immunity and airway cytokines while increasing the virulence of colonizing bacteria Journal of Molecular Medicine June 2016, Volume 94, Issue 6, pp 667–679 | Cite as John H. Hwang (1) (2) Matthew Lyes (1) (8) Katherine Sladewski (1) Shymaa Enany (3) (1) Elisa McEachern (1) (7) Denzil P. Mathew (1) Soumita Das (4) Alexander Moshensky (1) Sagar Bapat (5) David T. Pride (4) Weg M. Ongkeko (6) Laura E. Crotty Alexander (1) (2) Email author ([email protected]) 1. Pulmonary and Critical Care Section, VA San Diego Healthcare System, San Diego, USA 2. Department of Medicine, Division of Pulmonary and Critical Care, University of California at San Diego (UCSD), La Jolla, USA 3. Microbiology and Immunology Department, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt 4. Departments of Pathology and Medicine, UCSD, La Jolla, USA 5. Salk Institute for Biological Studies, La Jolla, USA 6. Division of Head and Neck Surgery, Department of Surgery, UCSD, La Jolla, USA 7. Weill Cornell Medical College, New York, USA 8. Duke University School of Medicine, Durham, USA Original Article First Online: 25 January 2016 Received: 10 August 2015 Revised: 27 November 2015 Accepted: 07 December 2015 90 Shares 2.3k Downloads 27 Citations

Abstract Electronic (e)-cigarette use is rapidly rising, with 20 % of Americans ages 25–44 now using these drug delivery devices. E-cigarette users expose their airways, cells of host defense, and colonizing bacteria to e-cigarette vapor (EV). Here, we report that exposure of human epithelial cells at the air– liquid interface to fresh EV (vaped from an e-cigarette device) resulted in dose-dependent cell death. After exposure to EV, cells of host defense— epithelial cells, alveolar macrophages, and neutrophils—had reduced antimicrobial activity against Staphylococcus aureus (SA). Mouse inhalation of EV for 1 h daily for 4 weeks led to alterations in inflammatory markers within the airways and elevation of an acute phase reactant in serum. Upon exposure to e-cigarette vapor extract (EVE), airway colonizer SA had increased biofilm formation, adherence and invasion of epithelial cells, resistance to human antimicrobial peptide LL-37, and up-regulation of virulence genes. EVE-exposed SA were more virulent in a mouse model of pneumonia. These data suggest that e-cigarettes may be toxic to airway cells, suppress host defenses, and promote inflammation over time, while also promoting virulence of colonizing bacteria.

Key message

Acute exposure to e-cigarette vapor (EV) is cytotoxic to airway cells in vitro. Acute exposure to EV decreases macrophage and neutrophil antimicrobial function. Inhalation of EV alters immunomodulating cytokines in the airways of mice. Inhalation of EV leads to increased markers of inflammation in BAL and serum. Staphylococcus aureus become more virulent when exposed to EV.

Keywords E-cigarette vapor Staphylococcal virulence Cytotoxicity Inflammatory lung disease Antimicrobial peptide LL-37 MRSA pneumonia

Electronic supplementary material The online version of this article (doi: 10.1007/s00109-016-1378-3 (https://doi.org/10.1007/s00109-016-1378-3)) contains supplementary material, which is available to authorized users. This is a preview of subscription content, log in to check access

Notes Acknowledgments This work was supported by the VA Career Development Award (CDA)-2, award no. 1IK2BX001313, PI Crotty Alexander, from the U.S. Department of Veterans Affairs, Biomedical Laboratory Research and Development (BLR&D) Program. Thank you to Drs. Ross Corriden and Simon Döhrmann for their technical support. Thank you to Dr. Atul Malhotra for his guidance and support.

Author contributions JHH, EM, WMO, SB, SD, and LCA designed the research. JHH, ML, KS, SE, SD, EM, DM, AM, SD, SB, WMO, and LCA performed the research and analyzed the data. JHH, SE, SB, ML, DTP, WMO, and LCA performed statistical analyses and edited the paper. JHH, SD, SB, and LCA wrote the paper.

Compliance with Ethical Standards Conflict of Interest The authors declare that they have no competing interests.

Supplementary material 109_2016_1378_MOESM1_ESM.pdf (1017 kb) ESM 1 (PDF 0.99 mb)

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About this article Cite this article as: Hwang, J.H., Lyes, M., Sladewski, K. et al. J Mol Med (2016) 94: 667. https://doi.org/10.1007/s00109-016-1378-3 DOI (Digital Object Identifier) https://doi.org/10.1007/s00109-016-1378-3 Publisher Name Springer Berlin Heidelberg Print ISSN 0946-2716 Online ISSN 1432-1440 About this journal Reprints and Permissions

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