Low-Dose Oxygen Enhances Macrophage-Derived Bacterial Clearance following Cigarette Smoke Exposure

Bain, William; Tripathi, Ashutosh; Mandke, Pooja; Gans, Jonathan H.; D’Alessio, Franco R.; Sidhaye, Venkataramana K.; Aggarwal, Neil R.

doi:10.1155/2016/1280347

Cited by 6 publications

(6 citation statements)

References 47 publications

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“…NTHi bacteria is the most common lung bacteria in COPD patient exacerbations (King 2012), and it is also common in cystic fibrosis (Bilton et al 1995) and chronic bronchitis patients (Bandi et al 2001). We and others have shown that smokers and COPD patient alveolar macrophages (Hodge et al 2007;Taylor et al 2010;Berenson et al 2013) as well as THP-1-differentiated macrophages and healthy control alveolar macrophages treated with CSE have decreased ability to phagocytose this bacteria (Bozinovski et al 2011;Hodge et al 2011;Thimmulappa et al 2012;Bain et al 2016;Ween et al 2016). Thus, we investigated whether E-cigarettes caused a similar phagocytic dysfunction utilizing our established THP-1 model.…”

Section: Discussionmentioning

confidence: 90%

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: Discussionmentioning

confidence: 90%

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

et al. 2017

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“…Inhaled fluticasone propionate has also been shown to impair pulmonary clearance of Klebsiella pneumoniae [ 63 ]. Treatment with lovastatin [ 64 ], low-dose oxygen [ 65 ], and the acute phase reactant α-1 antitrypsin [ 66 ] increased the efferocytosis function of LMs in a mouse model. Moreover, several studies have shown that statins beneficially impact innate immune responses in the lungs, including in subjects with COPD [ 67 ].…”

Section: Therapeutic Targeting Of Macrophages In Copdmentioning

confidence: 99%

Lung Macrophage Phenotypes and Functional Responses: Role in the Pathogenesis of COPD

Yamasaki

Eeden

2018

IJMS

103

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Lung macrophages (LMs) are essential immune effector cells that are pivotal in both innate and adaptive immune responses to inhaled foreign matter. They either reside within the airways and lung tissues (from early life) or are derived from blood monocytes. Similar to macrophages in other organs and tissues, LMs have natural plasticity and can change phenotype and function depending largely on the microenvironment they reside in. Phenotype changes in lung tissue macrophages have been implicated in chronic inflammatory responses and disease progression of various chronic lung diseases, including Chronic Obstructive Pulmonary Disease (COPD). LMs have a wide variety of functional properties that include phagocytosis (inorganic particulate matter and organic particles, such as viruses/bacteria/fungi), the processing of phagocytosed material, and the production of signaling mediators. Functioning as janitors of the airways, they also play a key role in removing dead and dying cells, as well as cell debris (efferocytic functions). We herein review changes in LM phenotypes during chronic lung disease, focusing on COPD, as well as changes in their functional properties as a result of such shifts. Targeting molecular pathways involved in LM phenotypic shifts could potentially allow for future targeted therapeutic interventions in several diseases, such as COPD.

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“…One aspect of CS-induced COPD-emphysema pathogenesis is constant bacterial colonization of the lower airways that provoke recurrent exacerbations in subjects causing high morbidity and mortality [ 2 , 49 – 51 ]. Studies have suggested that CS exposure impairs phagocytosis, which may account for these exacerbations [ 2 , 11 , 52 – 54 ]; however, the mechanism was unknown. Our studies first verified that CS exposure significantly impaired bacterial ( P. aeruginosa PA01-GFP) phagocytosis and improved its survival in murine macrophages.…”

Section: Discussionmentioning

confidence: 99%

Cigarette Smoke Exposure Inhibits Bacterial Killing via TFEB-Mediated Autophagy Impairment and Resulting Phagocytosis Defect

Pehote

Bodas

Brucia

et al. 2017

Mediators of Inflammation

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Introduction Cigarette smoke (CS) exposure is the leading risk factor for COPD-emphysema pathogenesis. A common characteristic of COPD is impaired phagocytosis that causes frequent exacerbations in patients leading to increased morbidity. However, the underlying mechanism is unclear. Hence, we investigated if CS exposure causes autophagy impairment as a mechanism for diminished bacterial clearance via phagocytosis by utilizing murine macrophages (RAW264.7 cells) and Pseudomonas aeruginosa (PA01-GFP) as an experimental model. Methods Briefly, RAW cells were treated with cigarette smoke extract (CSE), chloroquine (autophagy inhibitor), TFEB-shRNA, CFTR(inh)-172, and/or fisetin prior to bacterial infection for functional analysis. Results Bacterial clearance of PA01-GFP was significantly impaired while its survival was promoted by CSE (p < 0.01), autophagy inhibition (p < 0.05; p < 0.01), TFEB knockdown (p < 0.01; p < 0.001), and inhibition of CFTR function (p < 0.001; p < 0.01) in comparison to the control group(s) that was significantly recovered by autophagy-inducing antioxidant drug, fisetin, treatment (p < 0.05; p < 0.01; and p < 0.001). Moreover, investigations into other pharmacological properties of fisetin show that it has significant mucolytic and bactericidal activities (p < 0.01; p < 0.001), which warrants further investigation. Conclusions Our data suggests that CS-mediated autophagy impairment as a critical mechanism involved in the resulting phagocytic defect, as well as the therapeutic potential of autophagy-inducing drugs in restoring is CS-impaired phagocytosis.

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Low-Dose Oxygen Enhances Macrophage-Derived Bacterial Clearance following Cigarette Smoke Exposure

Cited by 6 publications

References 47 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

Lung Macrophage Phenotypes and Functional Responses: Role in the Pathogenesis of COPD

Cigarette Smoke Exposure Inhibits Bacterial Killing via TFEB-Mediated Autophagy Impairment and Resulting Phagocytosis Defect

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