Electronic cigarette exposure triggers neutrophil inflammatory responses

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Abstract

Background

The use of electronic cigarettes (e-cigs) is increasing and there is widespread perception that e-cigs are safe. E-cigs contain harmful chemicals; more research is needed to evaluate the safety of e-cig use. Our aim was to investigate the effects of e-cigs on the inflammatory response of human neutrophils.

Methods

Neutrophils were exposed to e-cig vapour extract (ECVE) and the expression of CD11b and CD66b was measured by flow cytometry and MMP-9 and CXCL8 by ELISA. We also measured the activity of neutrophil elastase (NE) and MMP-9, along with the activation of inflammatory signalling pathways. Finally we analysed the biochemical composition of ECVE by ultra-high performance liquid chromatography mass spectrometry.

Results

ECVE caused an increase in the expression of CD11b and CD66b, and increased the release of MMP-9 and CXCL8. Furthermore, there was an increase in NE and MMP-9 activity and an increase in p38 MAPK activation. We also identified several harmful chemicals in ECVE, including known carcinogens.

Conclusions

ECVE causes a pro-inflammatory response from human neutrophils. This raises concerns over the safety of e-cig use.

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-016-0368-x) contains supplementary material, which is available to authorized users.

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Most cited references 54

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The nature of small-airway obstruction in chronic obstructive pulmonary disease.

James C Hogg, Fanny Chu, Soraya Utokaparch … (2004)

Chronic obstructive pulmonary disease (COPD) is a major public health problem associated with long-term exposure to toxic gases and particles. We examined the evolution of the pathological effects of airway obstruction in patients with COPD. The small airways were assessed in surgically resected lung tissue from 159 patients--39 with stage 0 (at risk), 39 with stage 1, 22 with stage 2, 16 with stage 3, and 43 with stage 4 (very severe) COPD, according to the classification of the Global Initiative for Chronic Obstructive Lung Disease (GOLD). The progression of COPD was strongly associated with an increase in the volume of tissue in the wall (P<0.001) and the accumulation of inflammatory mucous exudates in the lumen (P<0.001) of the small airways. The percentage of the airways that contained polymorphonuclear neutrophils (P<0.001), macrophages (P<0.001), CD4 cells (P=0.02), CD8 cells (P=0.038), B cells (P<0.001), and lymphoid aggregates containing follicles (P=0.003) and the absolute volume of B cells (P=0.03) and CD8 cells (P=0.02) also increased as COPD progressed. Progression of COPD is associated with the accumulation of inflammatory mucous exudates in the lumen and infiltration of the wall by innate and adaptive inflammatory immune cells that form lymphoid follicles. These changes are coupled to a repair or remodeling process that thickens the walls of these airways. Copyright 2004 Massachusetts Medical Society

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Electronic cigarette: users profile, utilization, satisfaction and perceived efficacy.

Jean-François Etter, Chris Bullen (2011)

To assess the profile, utilization patterns, satisfaction and perceived effects among users of electronic cigarettes ('e-cigarettes'). Internet survey in English and French in 2010. Online questionnaire. Visitors of websites and online discussion forums dedicated to e-cigarettes and to smoking cessation. There were 3587 participants (70% former tobacco smokers, 61% men, mean age 41 years). The median duration of electronic cigarette use was 3 months, users drew 120 puffs/day and used five refills/day. Almost all (97%) used e-cigarettes containing nicotine. Daily users spent $33 per month on these products. Most (96%) said the e-cigarette helped them to quit smoking or reduce their smoking (92%). Reasons for using the e-cigarette included the perception that it was less toxic than tobacco (84%), to deal with craving for tobacco (79%) and withdrawal symptoms (67%), to quit smoking or avoid relapsing (77%), because it was cheaper than smoking (57%) and to deal with situations where smoking was prohibited (39%). Most ex-smokers (79%) feared they might relapse to smoking if they stopped using the e-cigarette. Users of nicotine-containing e-cigarettes reported better relief of withdrawal and a greater effect on smoking cessation than those using non-nicotine e-cigarettes. E-cigarettes were used much as people would use nicotine replacement medications: by former smokers to avoid relapse or as an aid to cut down or quit smoking. Further research should evaluate the safety and efficacy of e-cigarettes for administration of nicotine and other substances, and for quitting and relapse prevention. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.

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Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma.

V Keatings, P Collins, D. M. Scott … (1996)

Asthma and chronic obstructive pulmonary disease are characterized by chronic airway inflammation. Studies using bronchoalveolar lavage (BAL) have shown an increased proportion of eosinophils in the BAL fluid from asthmatics compared with that from normal subjects, whereas studies of chronic obstructive pulmonary disease (COPD) have shown increased numbers of neutrophils. Induced sputum allows sampling of respiratory tract secretions from patients and control subjects, providing a noninvasive method of studying airway secretions and allowing characterization of cells and measurement of soluble markers. We investigated whether induced sputum was a useful method of studying airway fluid from patients with moderate to severe COPD and whether it could be used to compare inflammation in this condition with that in asthma. An initial reproducibility study was undertaken. Sputum was induced twice in 13 patients with severe COPD at a 14-d interval. Total and differential cell counts were carried out and were found to be reproducible over this period. Sputum was then induced in 14 patients with COPD, 23 patients with asthma, 12 healthy cigarette smokers, and 16 normal nonsmoking control subjects. We found a significant increase in neutrophils and increased concentrations of tumor necrosis factor-alpha (TNF alpha) and interleukin-8 (IL-8) in the patients with COPD compared with the smoking and nonsmoking control subjects. Interleukin-8, but not TNF alpha, was significantly higher in the COPD group than in the asthmatic group. We conclude that the cytokines TNF alpha and IL-8 may be involved in the inflammation in COPD.

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Author and article information

Contributors

Andrew Higham: +44 (0) 161 291 5917 , +44 (0) 161 291 5806 , Andrew.Higham@manchester.ac.uk

Journal

Journal ID (nlm-ta): Respir Res

Journal ID (iso-abbrev): Respir. Res

Title: Respiratory Research

Publisher: BioMed Central (London )

ISSN (Print): 1465-9921

ISSN (Electronic): 1465-993X

Publication date (Electronic): 17 May 2016

Publication date PMC-release: 17 May 2016

Publication date (Print): 2016

Volume: 17

Electronic Location Identifier: 56

Affiliations

[ ]Manchester Academic Health and Science Centre, University Hospital of South Manchester Foundation Trust, Centre for Respiratory and Allergy Medicine, Institute of Inflammation and Repair, Faculty of Medical and Human Sciences, The University of Manchester, Manchester, UK

[ ]Manchester Institute of Biotechnology, School of Chemistry, The University of Manchester, Manchester, UK

Article

Publisher ID: 368

DOI: 10.1186/s12931-016-0368-x

PMC ID: 4869345

PubMed ID: 27184092

SO-VID: 874108e9-d3f5-4490-a0ad-0d872a3c54c6

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 21 October 2015

Date accepted : 27 February 2016

Funding

Funded by: North West Lung Centre Charity

Custom metadata

ScienceOpen disciplines: Respiratory medicine

Keywords: electronic cigarettes,copd,inflammation,smoking,neutrophils,mmp-9

Data availability:

ScienceOpen disciplines: Respiratory medicine

Keywords: electronic cigarettes, copd, inflammation, smoking, neutrophils, mmp-9

Electronic cigarette exposure triggers neutrophil inflammatory responses

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Abstract

Background

Methods

Results

Conclusions

Electronic supplementary material

Related collections

Biomarkers for Inflammatory Lung Disease

Most cited references 54

The nature of small-airway obstruction in chronic obstructive pulmonary disease.

Electronic cigarette: users profile, utilization, satisfaction and perceived efficacy.

Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma.

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