Nitrosative stress in the bronchial mucosa of severe chronic obstructive pulmonary disease

Ricciardolo, Fabio L. M.; Caramori, Gaetano; Itō, Kōji; Capelli, Arnaldo; Brun, Paola; Abatangelo, Giovanni; Papi, Alberto; Chung, Kian Fan; Adcock, Ian M.; Barnes, P. J.; Cf, Donner; Rossi, Anita De; Stefano, Antonino Di

doi:10.1016/j.rmedu.2006.01.016

Cited by 29 publications

(50 citation statements)

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“…These results are in agreement with the observed increased alveolar NO in patients with COPD [15]. In bronchial submucosa, there was also an effect of smoking, since smokers without airflow limitation had increased iNOS levels [16]. The expression of iNOS was increased in bronchial smooth muscle cells of patients with COPD and was correlated with the degree of airflow limitation [18].…”

Section: Chronic Obstructive Pulmonary Diseasesupporting

confidence: 88%

“…Remarkably, eNOS levels were significantly decreased in patients with severe COPD GOLD 4, probably caused by the destruction of the alveolar walls [10,19]. The levels of eNOS behaved similar to iNOS in bronchial submucosa [16].…”

Section: Chronic Obstructive Pulmonary Diseasementioning

confidence: 82%

“…In peripheral lung tissue and bronchial submucosa of patients with COPD, iNOS expression was significantly increased, irrespective of the GOLD stage [10,16]. Patients with severe COPD had increased iNOS þ cells in the alveolar wall and most of these cells were type II pneumocytes [17].…”

Section: Chronic Obstructive Pulmonary Diseasementioning

confidence: 98%

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Role of the nitric oxide–soluble guanylyl cyclase pathway in obstructive airway diseases

Dupont

Glynos²,

Bracke

et al. 2014

Pulmonary Pharmacology & Therapeutics

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a b s t r a c tNitric oxide (NO) is a gaseotransmitter, which is involved in many signaling processes in health and disease. Three enzymes generate NO from L-arginine, with citrulline formed as a by-product: neuronal NO synthase (nNOS or NOS1), endothelial NOS (eNOS or NOS3) and inducible NOS (iNOS or NOS2). NO is a ligand of soluble guanylyl cyclase (sGC), an intracellular heterodimer enzyme that catalyzes the conversion of guanosine triphosphate (GTP) to cyclic GMP (cGMP). cGMP further activates protein kinase G that eventually reduces the smooth muscle tone in bronchi or vessels. Phosphodiesterase 5 (PDE 5 ) degrades cGMP to GMP. However, NO reacts with superoxide anion (O À 2 ), leading to formation of the proinflammatory molecule peroxynitrite.Under physiological conditions, NO plays a homeostatic bronchoprotective role in healthy subjects. In obstructive airway diseases, NO can be beneficial by its bronchodilating effect, but could also be detrimental by the formation of peroxynitrite. Since asthma and COPD are associated with increased levels of exhaled NO, chronic inflammation and increased airway smooth muscle tone, the NO/sGC/cGMP pathway could be involved in these highly prevalent obstructive airway diseases. Here we review the involvement of NO, NO synthases, guanylyl cyclases, cGMP and phophodiesterase-5 in asthma and COPD and potential therapeutic approaches to modulate this pathway.

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Section: Chronic Obstructive Pulmonary Diseasesupporting

confidence: 88%

Section: Chronic Obstructive Pulmonary Diseasementioning

confidence: 82%

See 1 more Smart Citation

Role of the nitric oxide–soluble guanylyl cyclase pathway in obstructive airway diseases

Dupont

Glynos²,

Bracke

et al. 2014

Pulmonary Pharmacology & Therapeutics

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“…Increased levels of alveolar NO are measured in patients with severe chronic obstructive pulmonary disease, 5 whereas protein nitration is detected in the airway of such patients. 6 In line with these results, the expression of iNOS is exaggerated and is correlated with the extent of protein nitration in the alveolar walls of patients with pulmonary emphysema. 7 However, although markers of nitrosative stress are present in the lung of patients with emphysema, leading some authors to suggest a role for this phenomenon in the process of disease 6,[8][9][10] ; the relationship between nitrosative stress and the development of emphysema is unknown.…”

supporting

confidence: 66%

Role of nitric oxide synthases in elastase-induced emphysema

Boyer

Plantier

Dagouassat

et al. 2011

Laboratory Investigation

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Nitric oxide (NO) in combination with superoxide produces peroxynitrites and induces protein nitration, which participates in a number of chronic degenerative diseases. NO is produced at high levels in the human emphysematous lung, but its role in this disease is unknown. The aim of this study was to determine whether the NO synthases contribute to the development of elastase-induced emphysema in mice. nNOS, iNOS, and eNOS were quantified and immunolocalized in the lung after a tracheal instillation of elastase in mice. To determine whether eNOS or iNOS had a role in the development of emphysema, mice bearing a germline deletion of the eNOS and iNOS genes and mice treated with a pharmacological iNOS inhibitor were exposed to elastase. Protein nitration was determined by immunofluorescence, protein oxidation was determined by ELISA. Inflammation and MMP activity were quantified by cell counts, RT-PCR and zymography in bronchoalveolar lavage fluid. Cell proliferation was determined by Ki67 immunostaining. Emphysema was quantified morphometrically. iNOS and eNOS were diffusely upregulated in the lung of elastase-treated mice and a 12-fold increase in the number of 3-nitrotyrosine-expressing cells was observed. Over 80% of these cells were alveolar type 2 cells. In elastaseinstilled mice, iNOS inactivation reduced protein nitration and increased protein oxidation but had no effect on inflammation, MMP activity, cell proliferation or the subsequent development of emphysema. eNOS inactivation had no effect. In conclusion, in the elastase-injured lung, iNOS mediates protein nitration in alveolar type 2 cells and alleviates oxidative injury. Neither eNOS nor iNOS are required for the development of elastase-induced emphysema.

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“…Therefore, other hypotheses that account for the age-related decline in FeNO in smokers are also possible. Smoking-related downregulation of epithelial NOS2 enzyme activity and smoking-related increases in airway enzymes and reactive oxygen species that react with or metabolise NO are possible aetiologies for the age-related decline in FeNO in smokers [10,46]. Another hypothesis relates smoking-induced pulmonary changes due to COPD as the cause of decreased FeNO in smokers.…”

Section: Discussionmentioning

confidence: 99%

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

Sundy

Hauswirth²,

Mervin-Blake³

et al. 2007

European Respiratory Journal

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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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Nitrosative stress in the bronchial mucosa of severe chronic obstructive pulmonary disease

Cited by 29 publications

References 0 publications

Role of the nitric oxide–soluble guanylyl cyclase pathway in obstructive airway diseases

Role of the nitric oxide–soluble guanylyl cyclase pathway in obstructive airway diseases

Role of nitric oxide synthases in elastase-induced emphysema

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

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