Expression of Adhesion Molecules During Apoptosis of Circulating Neutrophils in COPD

Noguera, Aina; Sala, Ernest; Pons, A. R.; Iglesias, Julio; MacNee, William; Agustí, Àlvar

doi:10.1378/chest.125.5.1837

Cited by 45 publications

(44 citation statements)

References 25 publications

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“…Previous studies have shown that in vitro neutrophil apoptosis of blood neutrophils from subjects with COPD occurs at a similar rate as in healthy individuals and smokers with normal lung function [12], but is reduced during acute exacerbations of COPD and returns to levels seen in healthy control subjects within 2 weeks [13]. These observations are in keeping with studies showing reduced apoptosis of blood and bronchoalveolar lavage neutrophils in acute lung inflammation, such as respiratory distress syndrome, pneumonia [25,26] and exacerbations of bronchiectasis [27].…”

Section: Discussionmentioning

confidence: 90%

“…Two studies that examined the spontaneous apoptosis of peripheral blood neutrophils [12,13] found no difference in the rate of in vitro apoptosis of circulating neutrophils from subjects with stable COPD when compared with healthy smokers or healthy control subjects. The present authors have hypothesised that the presence of elevated concentrations of pro-neutrophil factors in the airways prolongs neutrophil survival, resulting in fewer apoptotic neutrophils being seen in the sputum of subjects with COPD.…”

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confidence: 99%

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Airway neutrophilia in COPD is not associated with increased neutrophil survival

Rytilä

Plataki²,

Bucchieri³

et al. 2006

European Respiratory Journal

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Neutrophilic airway inflammation is a prominent feature of chronic obstructive pulmonary disease (COPD) and correlates with disease severity. The mechanisms that determine the extent of neutrophilia could involve increased influx or prolonged survival of neutrophils. The aim of the study was to assess whether neutrophil pro-survival mechanisms are increased in the airways of subjects with COPD owing to the presence of anti-apoptotic factors in the bronchial lining fluid.Induced sputum samples were collected from 20 subjects with stable COPD, 14 healthy smokers and 14 healthy controls. Quantification of apoptotic neutrophils was based on typical morphological cell changes. Anti-apoptotic, pro-survival activity in the sputum was studied by culturing peripheral blood neutrophils with the fluid phase of induced sputum. Apoptosis was assessed both by morphology and flow cytometry using Annexin V/7-aminoactinomycin D staining.COPD patients and healthy smokers had significantly higher percentages of sputum neutrophils than healthy controls. However, there were no significant differences between the three subject groups in either the proportion of apoptotic neutrophils in sputum or the in vitro antiapoptotic activity detected in the sputum fluid phase.In conclusion, prolonged survival of neutrophils in sputum is not a feature of chronic obstructive pulmonary disease and cannot explain the increased numbers of airway neutrophils in this disease.

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Section: Discussionmentioning

confidence: 90%

mentioning

confidence: 99%

Airway neutrophilia in COPD is not associated with increased neutrophil survival

Rytilä

Plataki²,

Bucchieri³

et al. 2006

European Respiratory Journal

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“…However, increased levels of inflammatory chemokines and cytokines delay neutrophil apoptosis [31] and, in addition, the chronic inflammatory environment in the airway might inhibit the normal recognition mechanism whereby macrophages engulf apoptotic neutrophils [32]. Recent studies have shown that apoptosis is decreased in peripheral venous neutrophils from COPD patients during their exacerbations [33], while neutrophil apoptosis from COPD patients during its stable phase does not show differences versus neutrophils from healthy subjects [34]. In this work, early-onset COPD patients studied were in their stable phase, and we did not observe statistical differences in spontaneous apoptosis of isolated neutrophil versus healthy subjects, which is in line with previous studies on COPD [34].…”

Section: Discussionmentioning

confidence: 99%

Neutrophil Activation in Severe, Early-Onset COPD Patients versus Healthy Non-Smoker Subjects in vitro: Effects of Antioxidant Therapy

Milara¹,

Juan²,

Peiró³

et al. 2011

Respiration

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Background: Neutrophils and oxidative stress have been implicated in the pathogenesis of COPD. Severe, early-onset COPD is characterized by a rapid decline in the lung function at an early age; however, nothing is known about neutrophil activation in COPD patients. Objectives: The aim of this study was to evaluate peripheral blood neutrophil activation in severe, early-onset COPD patients versus healthy non-smokers and the effect of N-acetyl-L-cysteine (NAC) on neutrophil activation in vitro. Methods: Neutrophils were isolated from 15 severe, early-onset COPD patients and 15 age-matched healthy subjects and stimulated with N-formyl- Met-Leu-Phe (fMLP) in the presence or absence of NAC (10 µM to 10 mM). Neutrophil chemotaxis, elastase release, reactive oxygen species (ROS), intracellular thiols and apoptosis were measured by Boyden chamber, spectrofluorometry, CMFDA and H₂DCF-DA dyes and by annexin V-FITC, respectively. Results: Chemotaxis of peripheral blood neutrophils from COPD patients in response to fMLP was 30% more increased than that observed in healthy subjects. Elastase release in response to fMLP was 2-fold higher in neutrophils from COPD patients versus healthy subjects. Intracellular thiol levels were 30% lower in COPD and ROS was approximately 30% higher in COPD versus healthy neutrophils. Spontaneous apoptosis showed no differences in both groups of patients and fMLP-induced apoptosis was higher in COPD. Pre-treatment with the antioxidant NAC effectively attenuated neutrophil chemotaxis, elastase release and ROS as well as effectively increased thiol levels in COPD. Conclusions: Neutrophils in severe, early-onset COPD patients are highly activated and this is alleviated by NAC in vitro.

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“…Other studies have shown that circulating neutrophils from patients with COPD show upregulation of their surface adhesion molecules, which may also be an oxidant-mediated effect [6,30]. Activation may be even more pronounced in neutrophils which are sequestered in the pulmonary microcirculation in smokers and in patients with COPD, since these cells release more ROS than circulating neutrophils in animal models of lung inflammation [31].…”

Section: Oxidative Stress In Bloodmentioning

confidence: 99%

Oxidative stress and redox regulation of lung inflammation in COPD

Rahman

Adcock²

2006

European Respiratory Journal

770

599

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Reactive oxygen species, either directly or via the formation of lipid peroxidation products, may play a role in enhancing inflammation through the activation of stress kinases (cJun activated kinase, extracellular signal-regulated kinase, p38) and redox-sensitive transcription factors, such as nuclear factor (NF)-kB and activator protein-1. This results in increased expression of a battery of distinct pro-inflammatory mediators. Oxidative stress activates NF-kBmediated transcription of pro-inflammatory mediators either through activation of its activating inhibitor of kB-a kinase or the enhanced recruitment and activation of transcriptional coactivators. Enhanced NF-kB-co-activator complex formation results in targeted increases in histone modifications, such as acetylation leading to inflammatory gene expression.Emerging evidence suggests the glutathione redox couple may entail dynamic regulation of protein function by reversible disulphide bond formation on kinases, phosphatases and transcription factors. Oxidative stress also inhibits histone deacetylase activity and in doing so further enhances inflammatory gene expression and may attenuate glucocorticoid sensitivity.The antioxidant/anti-inflammatory effects of thiol molecules (glutathione, N-acetyl-L-cysteine and N-acystelyn, erdosteine), dietary polyphenols (curcumin-diferuloylmethane, cathechins/ quercetin and reserveratol), specific spin traps, such as a-phenyl-N-tert-butyl nitrone, a catalytic antioxidant (extracellular superoxide dismutase (SOD) mimetic, SOD mimetic M40419 and SOD, and catalase manganic salen compound, eukarion-8), porphyrins (AEOL 10150 and AEOL 10113) and theophylline have all been shown to play a role in either controlling NF-kB activation or affecting histone modifications with subsequent effects on inflammatory gene expression in lung epithelial cells.Thus, oxidative stress regulates both key signal transduction pathways and histone modifications involved in lung inflammation. Various approaches to enhance lung antioxidant capacity and clinical trials of antioxidant compounds in chronic obstructive pulmonary disease are also discussed.

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Expression of Adhesion Molecules During Apoptosis of Circulating Neutrophils in COPD

Cited by 45 publications

References 25 publications

Airway neutrophilia in COPD is not associated with increased neutrophil survival

Airway neutrophilia in COPD is not associated with increased neutrophil survival

Neutrophil Activation in Severe, Early-Onset COPD Patients versus Healthy Non-Smoker Subjects in vitro: Effects of Antioxidant Therapy

Oxidative stress and redox regulation of lung inflammation in COPD

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