Patterns of Inflammatory Responses in Large and Small Airways in Smokers with and without Chronic Obstructive Pulmonary Disease

Isajevs, Sergejs; Taivāns, Immanuels; Svirina, Darja; Strazda, Gunta; Kopeika, Uldis

doi:10.1159/000322560

Cited by 41 publications

(35 citation statements)

References 50 publications

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“…In accordance with previous studies [30,31,32,33], we observed a higher density of alveolar CD8+ cells and macrophages in COPD patients. Few studies have investigated the relationship between inflammation and AHR in COPD.…”

Section: Discussionsupporting

confidence: 93%

Cholinergic Hyperresponsiveness of Peripheral Lung Parenchyma in Chronic Obstructive Pulmonary Disease

et al. 2011

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Background: Up to 60% of chronic obstructive pulmonary disease (COPD) patients can present airway hyperresponsiveness. However, it is not known whether the peripheral lung tissue also shows an exaggerated response to agonists in COPD. Objectives: To investigate the in vitro mechanical behavior and the structural and inflammatory changes of peripheral lung tissue in COPD patients and compare to nonsmoking controls. Methods: We measured resistance and elastance at baseline and after acetylcholine (ACh) challenge of lung strips obtained from 10 COPD patients and 10 control subjects. We also assessed the alveolar tissue density of neutrophils, eosinophils, macrophages, mast cells and CD8+ and CD4+ cells, as well as the content of α-smooth muscle actin-positive cells and elastic and collagen fibers. We further investigated whether changes in in vitro parenchymal mechanics correlated to structural and inflammatory parameters and to in vivo pulmonary function. Results: Values of resistance after ACh treatment and the percent increase in tissue resistance (%R) were higher in the COPD group (p ≤ 0.03). There was a higher density of macrophages and CD8+ cells (p < 0.05) and a lower elastic content (p = 0.003) in the COPD group. We observed a positive correlation between %R and eosinophil and CD8+ cell density (r = 0.608, p = 0.002, and r = 0.581, p = 0.001, respectively) and a negative correlation between %R and the ratio of forced expiratory volume in 1 s to forced vital capacity (r = –0.451, p < 0.05). Conclusions: The cholinergic responsiveness of parenchymal lung strips is increased in COPD patients and seems to be related to alveolar tissue eosinophilic and CD8 lymphocytic inflammation and to the degree of airway obstruction on the pulmonary function test.

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Section: Discussionsupporting

confidence: 93%

Cholinergic Hyperresponsiveness of Peripheral Lung Parenchyma in Chronic Obstructive Pulmonary Disease

et al. 2011

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“…As oxidative stress is highly related with the progression and consequently with the exacerbations of this disease, the use of antioxidants is likely to have a beneficial outcome [12]. The antioxidant agent N-acetyl- L -cysteine (NAC) inhibits oxidative stress changing the cellular redox status and acting as a direct reactive oxygen species (ROS) scavenger.…”

Section: Introductionmentioning

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

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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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“…There is convincing evidence that neutrophils are one of the primary effector cells in COPD [3,4,5,6,7]. The number of neutrophils is increased in bronchoalveolar lavage fluid as well as in induced sputum samples and airways from COPD patients [6,8,9]. The amount of neutrophils correlates with disease severity and progression in these patients [3,8].…”

Section: Introductionmentioning

confidence: 99%

Bronchoepithelial Expression of CXCR1 and CXCR2 Does Not Facilitate Transepithelial Migration of Neutrophils

et al. 2011

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Background: Neutrophilic airway inflammation is one of the key features of chronic obstructive pulmonary disease (COPD). The chemokine receptors 1 (CXCR1) and 2 (CXCR2) are expressed in the bronchial mucosa during chronic inflammation and might be of importance for transepithelial migration of neutrophils. Objectives: This study addressed the role of bronchoepithelial CXCR1 and CXCR2 expression with respect to transepithelial migration of neutrophils. Methods: Primary bronchial epithelial cells (PBECs) derived from COPD patients and healthy controls as well as transiently CXCR1- and CXCR2-transfected Calu-6 cells were used for transepithelial migration assays of neutrophils under various conditions. Epithelial CXCR1 and CXCR2 expression was verified by means of flow cytometry. Results: Transepithelial migration of neutrophils was significantly increased following lipopolysaccharide pretreatment of epithelial cells. Transient transfection of CXCR1 and CXCR2 neither augmented the transepithelial migration of neutrophils, nor did the selective blockade of CXCR1 and CXCR2 have any significant effect on neutrophilic transepithelial migration. In addition, no differences were found in PBECs and neutrophils derived from healthy controls and COPD patients. Conclusions: The data of the present study do not support the hypothesis that bronchoepithelial expression of CXCR1 and/or CXCR2 facilitate transepithelial migration of neutrophils.

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Patterns of Inflammatory Responses in Large and Small Airways in Smokers with and without Chronic Obstructive Pulmonary Disease

Cited by 41 publications

References 50 publications

Cholinergic Hyperresponsiveness of Peripheral Lung Parenchyma in Chronic Obstructive Pulmonary Disease

Cholinergic Hyperresponsiveness of Peripheral Lung Parenchyma in Chronic Obstructive Pulmonary Disease

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

Bronchoepithelial Expression of CXCR1 and CXCR2 Does Not Facilitate Transepithelial Migration of Neutrophils

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