Cigarette smoke (CS) and nicotine delay neutrophil spontaneous death via suppressing production of diphosphoinositol pentakisphosphate

Xu, Yuanfu; Li, Hongmei; Bajrami, Besnik; Kwak, Hyun-Jeong; Cao, Shengnan; Liu, Peng; Zhou, Jiaxi; Zhou, Yuan; Zhu, Haiyan; Ye, Keqiang; Luo, Hongbo

doi:10.1073/pnas.1302906110

Cited by 47 publications

(42 citation statements)

References 38 publications

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“…Nicotine hinders the hydration of mucus,28 promotes Ca 2+ influx in airway smooth muscle cells,29 blocks neutrophil apoptosis30 and induces pro-inflammatory dendritic cell responses 31. Smoke generated from high-dose nicotine cigarettes induces more emphysematous changes than low-dose nicotine cigarettes, in elastase-treated rats 32.…”

Section: Discussionmentioning

confidence: 99%

Chronic electronic cigarette exposure in mice induces features of COPD in a nicotine-dependent manner

García-Arcos

Geraghty

Baumlin

et al. 2016

Thorax

276

263

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BackgroundThe use of electronic (e)-cigarettes is increasing rapidly, but their lung health effects are not established. Clinical studies examining the potential long-term impact of e-cigarette use on lung health will take decades. To address this gap in knowledge, this study investigated the effects of exposure to aerosolised nicotine-free and nicotine-containing e-cigarette fluid on mouse lungs and normal human airway epithelial cells.MethodsMice were exposed to aerosolised phosphate-buffered saline, nicotine-free or nicotine-containing e-cigarette solution, 1-hour daily for 4 months. Normal human bronchial epithelial (NHBE) cells cultured at an air-liquid interface were exposed to e-cigarette vapours or nicotine solutions using a Vitrocell smoke exposure robot.ResultsInhalation of nicotine-containing e-cigarettes increased airway hyper-reactivity, distal airspace enlargement, mucin production, cytokine and protease expression. Exposure to nicotine-free e-cigarettes did not affect these lung parameters. NHBE cells exposed to nicotine-containing e-cigarette vapour showed impaired ciliary beat frequency, airway surface liquid volume, cystic fibrosis transmembrane regulator and ATP-stimulated K+ ion conductance and decreased expression of FOXJ1 and KCNMA1. Exposure of NHBE cells to nicotine for 5 days increased interleukin (IL)-6 and IL-8 secretion.ConclusionsExposure to inhaled nicotine-containing e-cigarette fluids triggered effects normally associated with the development of COPD including cytokine expression, airway hyper-reactivity and lung tissue destruction. These effects were nicotine-dependent both in the mouse lung and in human airway cells, suggesting that inhaled nicotine contributes to airway and lung disease in addition to its addictive properties. Thus, these findings highlight the potential dangers of nicotine inhalation during e-cigarette use.

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Section: Discussionmentioning

confidence: 99%

Chronic electronic cigarette exposure in mice induces features of COPD in a nicotine-dependent manner

García-Arcos

Geraghty

Baumlin

et al. 2016

Thorax

276

263

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“…A potential reason for their continued presence may be due to impaired cell death of the neutrophils. Cigarette smoke hinders spontaneous neutrophil cell death by blocking Akt deactivation via suppression of diphosphoinositol pentakisphosphate production (45), thus dysregulation of neutrophil cell death may account for their persistence in the lungs and contribute to the chronic inflammation mediated by cigarette smoke.…”

Section: Discussionmentioning

confidence: 99%

Cigarette Smoke Exposure Exacerbates Lung Inflammation and Compromises Immunity to Bacterial Infection

Lugade

Bogner

Thatcher

et al. 2014

The Journal of Immunology

114

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The detrimental impact of tobacco on human health is clearly recognized and despite aggressive efforts to prevent smoking, close to one billion individuals worldwide continue to smoke. People with chronic obstructive pulmonary disease (COPD) are susceptible to recurrent respiratory infections with pathogens, including non-typeable Haemophilus influenzae (NTHI), yet the reasons for this increased susceptibility are poorly understood. As mortality rapidly increases with multiple exacerbations, development of protective immunity is critical to improving patient survival. Acute NTHI infection has been studied in the context of cigarette smoke exposure, but this is the first study to investigate chronic infection and the generation of adaptive immune responses to NTHI following chronic smoke exposure. After chronic NTHI infection, mice that had previously been exposed to cigarette smoke developed increased lung inflammation and compromised adaptive immunity relative to air-exposed controls. Importantly, NTHI-specific T cells from mice exposed to cigarette smoke produced lower levels of IFN-γ and IL-4, and B cells produced reduced levels of antibodies against outer membrane lipoprotein P6, with impaired IgG1, IgG2a and IgA class-switching. However, production of IL-17, which is associated with neutrophilic inflammation, was enhanced. Interestingly, cigarette smoke exposed mice exhibited a similar defect in the generation of adaptive immunity following immunization with P6. Our study has conclusively demonstrated that cigarette smoke exposure has a profound suppressive effect on the generation of adaptive immune responses to NTHI and suggests the mechanism by which prior cigarette smoke exposure predisposes COPD patients to recurrent infections, leading to exacerbations and contributing to mortality.

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“…CS and nicotine seem to delay neutrophil death, contributing to the pathogenesis of the disease. Spontaneous modifying neutrophil death provides an important treatment strategy in tobaccoinduced COPD [112].…”

Section: Treatmentmentioning

confidence: 99%

Neutrophils and emerging targets for treatment in chronic obstructive pulmonary disease

Meijer

Rijkers

Overveld

2013

Expert Review of Clinical Immunology

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Chronic obstructive pulmonary disease (COPD) is characterized by a decreased airflow due to airway narrowing that, once it occurs, is not fully reversible. The disease usually is progressive and associated with an enhanced inflammatory response in the lungs after exposure to noxious particles or gases. After removal of the noxious particles, the inflammation can continue in a self-sustaining manner. It has been established that improper activation of neutrophils lies at the core of the pathology. This paper provides an overview of the mechanisms by which neutrophils can induce the pulmonary damage of COPD. As the pathogenesis of COPD is slowly being unraveled, new points of intervention are discovered, some of which with promising results.

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Cigarette smoke (CS) and nicotine delay neutrophil spontaneous death via suppressing production of diphosphoinositol pentakisphosphate

Cited by 47 publications

References 38 publications

Chronic electronic cigarette exposure in mice induces features of COPD in a nicotine-dependent manner

Chronic electronic cigarette exposure in mice induces features of COPD in a nicotine-dependent manner

Cigarette Smoke Exposure Exacerbates Lung Inflammation and Compromises Immunity to Bacterial Infection

Neutrophils and emerging targets for treatment in chronic obstructive pulmonary disease

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