Epithelial Permeability, Inflammation, and Oxidant Stress in the Air Spaces of Smokers

Morrison, Douglas; Rahman, Irfan; Lannan, S.; MacNee, William

doi:10.1164/ajrccm.159.2.9804080

Cited by 255 publications

(194 citation statements)

References 31 publications

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“…We, and others, have shown that leukocytes isolated from patients with COPD release high levels of O 2 ⅐ , 15,16 which was associated with increased systemic levels of inflammatory mediators. 17,18 Hence, inhibition of CS-induced generation of ROS would confer protection against oxidantmediated lung inflammation.…”

Section: Cigarette Smoke (Cs) Induces Recruitment Of Inflammatory Celmentioning

confidence: 79%

“…19 -22,50,51 We, and others, have shown that O 2 ⅐Ϫ release is increased from leukocytes isolated from smokers and in patients with COPD, 15,16 as well as from endothelial cells in response to CS that is mediated via NADPH oxidase activation. 11,12 However, the role of NADPH oxidase in CS-induced lung inflammation is not known.…”

Section: Discussionmentioning

confidence: 95%

“…Patients with COPD have increased levels of proinflammatory mediators, such as IL-6, TNF-␣, KC, MCP-1, and GM-CSF in the lungs. 1,15,18 It is known that the ROS generated by NADPH oxidase can activate NF-B, leading to NF-Bdependent release of proinflammatory cytokines. Therefore, we investigated whether p47 phoxϪ/Ϫ and gp91 phoxϪ/Ϫ mice exhibited the altered levels of cytokines/chemokines, which were measured by Luminex multiplex assay in lung homogenates in response to both acute and subchronic CS exposures.…”

Section: Genetic Ablation Of P47 Phox and Gp91 Phox Enhanced Inflammamentioning

confidence: 99%

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Genetic Ablation of NADPH Oxidase Enhances Susceptibility to Cigarette Smoke-Induced Lung Inflammation and Emphysema in Mice

Yao

Edirisinghe

Yang

et al. 2008

The American Journal of Pathology

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Cigarette smoke (CS) induces recruitment of inflammatory cells in the lungs leading to the generation of reactive oxygen species (ROS), which are involved in lung inflammation and injury. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is a multimeric system that is responsible for ROS production in mammalian cells. We hypothesized that NADPH oxidase-derived ROS play an important role in lung inflammation and injury and that targeted ablation of components of NADPH oxidase (p47 phox and gp91 phox ) would protect lungs against the detrimental effects of CS. To test this hypothesis, we exposed p47 phox؊/؊ and gp91 phox؊/؊ mice to CS and examined inflammatory response and injury in the lung. Surprisingly, although CS-induced ROS production was decreased in the lungs of p47 phox؊/؊ and gp91 phox؊/؊ mice compared with wild-type mice, the inflammatory response was significantly increased and was accompanied by development of distal airspace enlargement and alveolar destruction. This pathological abnormality was associated with enhanced activation of the TLR4-nuclear factor-B pathway in response to CS exposure in p47 phox؊/؊ and gp91 phox؊/؊ mice. This phenomenon was confirmed by in vitro studies in which treatment of peritoneal macrophages with a nuclear factor-B inhibitor reversed the CS-induced release of proinflammatory mediators. Thus, these data suggest that genetic ablation of components of NADPH oxidase enhances susceptibility to the proinflammatory effects of CS leading to airspace enlargement and alveolar damage.

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Section: Cigarette Smoke (Cs) Induces Recruitment Of Inflammatory Celmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 95%

Section: Genetic Ablation Of P47 Phox and Gp91 Phox Enhanced Inflammamentioning

confidence: 99%

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Genetic Ablation of NADPH Oxidase Enhances Susceptibility to Cigarette Smoke-Induced Lung Inflammation and Emphysema in Mice

Yao

Edirisinghe

Yang

et al. 2008

The American Journal of Pathology

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“…42 Human studies have shown elevated levels of GSH in epithelial lining fluid in chronic cigarette smokers compared to non-smokers. 42,43 Enzymatic antioxidant defences include SOD, catalase, thioredoxin, Gpx, and glutathione-S-transferase. Bronchial epithelial cells of rats exposed to cigarette smoke have shown increased expression of the antioxidant genes manganese superoxide dismutase, metallothionein, and Gpx.…”

Section: Endogenous Antioxidant Defences Within the Lungmentioning

confidence: 99%

Glutathione peroxidase-1 as a novel therapeutic target for COPD

Vlahos

Bozinovski

2013

Redox Report

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Oxidative stress plays a role in a variety of diseases but it is even more pertinent in chronic obstructive pulmonary disease (COPD) given the increased oxidant burden in smokers. The increased oxidant burden results from the fact that cigarette smoke contains over 4700 different chemical compounds and more than 10 15 oxidants/free radicals per puff. Other factors, such as air pollutants, infections, and occupational dusts that may exacerbate COPD, also have the potential to produce oxidative stress. These oxidants give rise to Reactive Oxygen Species (ROS) that are generated enzymatically by inflammatory and epithelial cells within the lung as part of an inflammatory immune response towards a pathogen or irritant. Thus, while ROS are necessary for host defence against invading pathogens, increased levels of ROS have been implicated in initiating inflammatory responses in the lungs through the activation of transcriptional factors, signal transduction pathways, chromatin remodelling and gene expression of proinflammatory mediators. However, the normal lung has developed defences to ROS-mediated damage, which include antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. In this review we consider the therapeutic potential of the antioxidant enzyme glutathione peroxidase-1 for the treatment of cigarette smoke-induced lung inflammation and damage.

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“…The increased synthesis of nitric oxide may be caused by activation of inducible NO-synthase which is expressed in macrophages, neutrophils, mast cells, endothelial, epithelial cells and smooth muscle cells [16,34]. The increased formation of NO-metabolites in the respiratory tract in COPD can result from the effects of such factors as pathogenic bacteria and viruses, the inhalation of a range of exogenous compounds including cigarette smoke, nitrogen dioxide and fine particles [35][36][37]. Furthermore, it has been shown [38,39] that the increase in the amount of nitric oxide products is associated with increased hypoxia in patients with severe COPD.…”

mentioning

confidence: 99%

The Significance of Soluble Molecules of Cellular Adhesion, Nitric Oxide Metabolites, and Endothelin-1 and Their Associations as Markers of Progression of Inflammation in COPD

Kubysheva¹,

Postnikova²,

Soodaeva³

et al. 2017

Sovrem Tehnol Med

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The aim of the investigation was to assess the significance of the content of metabolites of the nitric oxide, sICAM-1 and sICAM-3 in blood serum and in exhaled breath condensate, the serum level of endothelin-1 as systemic and topical markers of inflammation in patients with COPD, and their correlations with the parameters of lung ventilation function. Materials and Methods. 91 patients with COPD, aged from 46 to 67, and 21 healthy, non-smoking volunteers took part in the study. The material for investigation was blood serum and exhaled breath condensate.Results. The severity of progression of COPD was linked with an increase in the serum content of sCD50, sCD54, ET-1, as well as in the concentrations of metabolites of nitric oxide in blood and in exhaled breath condensate. For the patients with COPD we determined the associations between the function of pulmonary ventilation and the levels of ET-1, sICAM-1, sICAM-3 and the value of ΣNO 2 -/NO 3 -. The resulting correlations between the concentration of soluble adhesion molecules, the values of nitrosative stress, and ET-1 level indicate that they are involved in the genesis of chronic inflammation in COPD patients.Key words: chronic obstructive pulmonary disease; COPD; endothelin-1; ET-1; nitrosative stress; soluble molecules of adhesion ICAM-1 and ICAM-3; exhaled breath condensate. Markers of progression of inflammation in COpDThe steady increase in the prevalence of chronic obstructive pulmonary disease (COPD) and the mortality rate associated with this pathology indicate the importance of studying the pathogenic mechanisms of development of this disease [1]. The identification of new activity markers and the progression of inflammation are key tasks in the studies of these mechanisms.The result of the immune-mediated mechanisms of inflammation in response to damaging factors is the excessive migration of effector cells to the

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Epithelial Permeability, Inflammation, and Oxidant Stress in the Air Spaces of Smokers

Cited by 255 publications

References 31 publications

Genetic Ablation of NADPH Oxidase Enhances Susceptibility to Cigarette Smoke-Induced Lung Inflammation and Emphysema in Mice

Genetic Ablation of NADPH Oxidase Enhances Susceptibility to Cigarette Smoke-Induced Lung Inflammation and Emphysema in Mice

Glutathione peroxidase-1 as a novel therapeutic target for COPD

The Significance of Soluble Molecules of Cellular Adhesion, Nitric Oxide Metabolites, and Endothelin-1 and Their Associations as Markers of Progression of Inflammation in COPD

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