Investigating the impact of electronic cigarettes on neutrophil function

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Jasper, Alice E ORCID: https://orcid.org/0000-0001-9294-1200 (2022). Investigating the impact of electronic cigarettes on neutrophil function. University of Birmingham. Ph.D.

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Abstract

Electronic (e-) cigarettes were developed in the early 2000s as safer alternatives to tobacco smoking. Their popularity continues to rise amongst current smokers, ex-smokers and never smokers despite uncertainties in their long-term safety. Studies have begun to uncover early indicators of potential harm including changes in function, transcription, and communication of important cells of the respiratory immune system.
This thesis aimed to investigate the impact of e-cigarette vapour on neutrophil functions and uncover potential drivers of dysfunction. A novel and adaptable model of direct e-cigarette vapour exposure was developed, validated, and applied to the treatment of human peripheral blood neutrophils. Neutrophils were isolated from the whole blood of otherwise healthy non-smokers/non-vapers and exposed to e-cigarette vapour. Two generations of e-cigarette device, along with two e-liquids of different nicotine strengths were tested, to understand the contribution of device power and nicotine content to the neutrophil functions examined.
Key neutrophil effector functions including chemotaxis, transmigration, phagocytosis, and oxidative burst were blunted by e-cigarette vapour exposure. In all cases, higher-powered e-cigarette devices had a more inhibitory effect on neutrophil functions. Nicotine-free e-cigarette vapour prevented key neutrophil effect functions including phagocytosis and transmigration, indicating this effect cannot only be attributed to nicotine. To understand the mechanistic drivers of these changes, neutrophil transcriptome, metabolism (glycolytic function), and calcium signalling were explored. In addition, neutrophils were pre-treated with a nicotinic receptor inhibitor,
phosphoinositide 3-kinase (Pi3K) inhibitors and the antioxidant and anti-aldehyde agent N-acetyl cysteine (NAC), and the ability to restore e-cigarette-induced dysfunction was assessed. Pre-treatment of neutrophils with NAC appeared to provide the greatest protection against e-cigarette vapour-induced dysfunctional phagocytosis and transmigration, providing rationale for this effect to be further elucidated.
Overall, this thesis demonstrated e-cigarette vapour-induced neutrophil dysfunction, which could have persistent consequences for lung health, and raises concerns over the long-term safety of e-cigarette use.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):