Increased airway epithelial and T-cell apoptosis in COPD remains despite smoking cessation

Hodge, Sandra; Hodge, Greg; Holmes, Mark; Reynolds, Paul N.

doi:10.1183/09031936.05.00077604

Cited by 224 publications

(191 citation statements)

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“…Our identification of defective alveolar macrophage phagocytic function in chronic obstructive disease (COPD) subjects and in response to cigarette smoke (especially with regard to the clearance of apoptotic material, termed efferocytosis), lead to the subsequent discovery of significantly increased apoptosis of epithelial cells in the airway of chronic obstructive pulmonary disease (COPD) subjects and cigarette smokers (Hodge et al. 2005; Hodge et al. 2007; Tran et al.…”

Section: Introductionmentioning

confidence: 99%

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Phagocytosis and Inflammation: Exploring the effects of the components of E-cigarette vapor on macrophages

et al. 2017

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E‐cigarettes are perceived as harmless; however, evidence of their safety is lacking. New data suggests E‐cigarettes discharge a range of compounds capable of physiological damage to users. We previously established that cigarette smoke caused defective alveolar macrophage phagocytosis. The present study compared the effect E‐cigarette of components; E‐liquid flavors, nicotine, vegetable glycerine, and propylene glycol on phagocytosis, proinflammatory cytokine secretion, and phagocytic recognition molecule expression using differentiated THP‐1 macrophages. Similar to CSE, phagocytosis of NTHi bacteria was significantly decreased by E‐liquid flavoring (11.65–15.75%) versus control (27.01%). Nicotine also decreased phagocytosis (15.26%). E‐liquid, nicotine, and E‐liquid+ nicotine reduced phagocytic recognition molecules; SR‐A1 and TLR‐2. IL‐8 secretion increased with flavor and nicotine, while TNF α, IL‐1β, IL‐6, MIP‐1α, MIP‐1β, and MCP‐1 decreased after exposure to most flavors and nicotine. PG, VG, or PG:VG mix also induced a decrease in MIP‐1α and MIP‐1β. We conclude that E‐cigarettes can cause macrophage phagocytic dysfunction, expression of phagocytic recognition receptors and cytokine secretion pathways. As such, E‐cigarettes should be treated with caution by users, especially those who are nonsmokers.

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Section: Introductionmentioning

confidence: 99%

“…These findings implicate defective efferocytosis with secondary necrosis and potentiation of the inflammatory milieu (Hodge et al. 2003, 2005). …”

Section: Introductionmentioning

confidence: 99%

Phagocytosis and Inflammation: Exploring the effects of the components of E-cigarette vapor on macrophages

et al. 2017

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“…For example, several animal models of COPD are associated with increased accumulation (58 -61) and impaired removal (45) of apoptotic cells. Likewise, apoptotic cells are increased in COPD lungs (31,(62)(63)(64)(65) and efferocytosis is defective in COPD alveolar macrophages ex vivo (32). Therefore, we tested the effect of lovastatin on efferocytosis by alveolar macrophages isolated from GOLD stage 2 (66) COPD patients (Table I).…”

Section: Lovastatin Enhances Efferocytosis By Human Alveolar Macrophamentioning

confidence: 99%

Lovastatin Enhances Clearance of Apoptotic Cells (Efferocytosis) with Implications for Chronic Obstructive Pulmonary Disease

Morimoto

Janssen²,

Fessler³

et al. 2006

The Journal of Immunology

200

179

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Statins are potent, cholesterol-lowering agents with newly appreciated, broad anti-inflammatory properties, largely based upon their ability to block the prenylation of Rho GTPases, including RhoA. Because phagocytosis of apoptotic cells (efferocytosis) is a pivotal regulator of inflammation, which is inhibited by RhoA, we sought to determine whether statins enhanced efferocytosis. The effect of lovastatin on efferocytosis was investigated in primary human macrophages, in the murine lung, and in human alveolar macrophages taken from patients with chronic obstructive pulmonary disease. In this study, we show that lovastatin increased efferocytosis in vitro in an 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase-dependent manner. Lovastatin acted by inhibiting both geranylgeranylation and farnesylation, and not by altering expression of key uptake receptors or by increasing binding of apoptotic cells to phagocytes. Lovastatin appeared to exert its positive effect on efferocytosis by inhibiting RhoA, because it 1) decreased membrane localization of RhoA, to a greater extent than Rac-1, and 2) prevented impaired efferocytosis by lysophosphatidic acid, a potent inducer of RhoA. Finally, lovastatin increased efferocytosis in the naive murine lung and ex vivo in chronic obstructive pulmonary disease alveolar macrophages in an HMG-CoA reductase-dependent manner. These findings indicate that statins enhance efferocytosis in vitro and in vivo, and suggest that they may play an important therapeutic role in diseases where efferocytosis is impaired and inflammation is dysregulated.

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“…FeNO levels increase after smoking cessation but not to normal levels [2,6,10], which suggests that smoking-related declines in FeNO may be associated with permanent lung damage. As respiratory epithelium is the likely source of most FeNO [11][12][13][14][15] and is damaged by chronic smoke exposure [16][17][18][19][20], smoking-related declines in FeNO may be a marker of airway epithelial damage.…”

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confidence: 99%

Smoking is associated with an age-related decline in exhaled nitric oxide

Sundy

Hauswirth²,

Mervin-Blake³

et al. 2007

Eur Respir J

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Age-related declines in forced expiratory volume in one second are accelerated in smokers. Smoking is associated with decreased exhaled nitric oxide fraction (FeNO). The aim of the present study was to determine the impact of age on FeNO in otherwise healthy smokers and nonsmokers.FeNO and serum cotinine levels were measured in 994 healthy subjects aged 18-40 yrs. American Thoracic Society questionnaire data on smoking habits was used to validate serum cotinine levels as a surrogate marker for categorisation of smokers and nonsmokers in the cohort.Serum cotinine levels were a good discriminator of smokers (n599) and nonsmokers (n5895). FeNO levels were significantly lower in otherwise healthy smokers compared with nonsmokers. There was an inverse correlation of serum cotinine levels with FeNO. No correlation of age with FeNO was found in nonsmokers but an inverse correlation of FeNO with age in smokers was found. FeNO was significantly lower in smokers aged 21-40 yrs compared with nonsmokers aged 21-40 yrs, but was not lower in smokers aged 18-20 yrs compared with nonsmokers of the same age.Smoking was associated with decreased exhaled nitric oxide. The greatest smoking-related declines in exhaled nitric oxide occurred in older subjects. This suggests that smoking is associated with age-related declines in exhaled nitric oxide and justifies future mechanistic studies that address the impact of exhaled nitric oxide decline on lung function.

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Increased airway epithelial and T-cell apoptosis in COPD remains despite smoking cessation

Cited by 224 publications

References 43 publications

Phagocytosis and Inflammation: Exploring the effects of the components of E-cigarette vapor on macrophages

Phagocytosis and Inflammation: Exploring the effects of the components of E-cigarette vapor on macrophages

Lovastatin Enhances Clearance of Apoptotic Cells (Efferocytosis) with Implications for Chronic Obstructive Pulmonary Disease

Smoking is associated with an age-related decline in exhaled nitric oxide

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