Pulmonary dysfunction in cystic fibrosis is associated with oxidative stress

Brown, RK; Wyatt, Hilary; Price, Jackie F.; Kelly, Frank J.

doi:10.1183/09031936.96.09020334

Cited by 148 publications

(80 citation statements)

References 30 publications

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“…Cystic fibrosis patients also have increased oxidative stress [23] due to neutrophils [24] and consequently have been shown to have lower levels of antioxidants in the circulation [25,26]. Studies on isolated neutrophils from the peripheral blood of CF patients have shown a different response pattern to inflammatory mediators and stimulants to that seen in neutrophils from normals [10,11,27].…”

Section: Discussionmentioning

confidence: 99%

Effect of cystic fibrosis exacerbations on neutrophil function

Brockbank

Downey

Elborn

et al. 2005

International Immunopharmacology

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In cystic fibrosis (CF), inflammation is caused by persistent bacterial infection from Pseudomonas aeruginosa and Burkholderia cenocepacia in the lung and is characterised by the persistent infiltration of massive numbers of neutrophils which leads to lung injury. The aim of this present study was to investigate the effects of CF exacerbations on the reactivity of peripheral blood neutrophils compared to data from a normal healthy control population. Peripheral blood neutrophils were isolated from control subjects and CF patients before and after an exacerbation of their lung disease. Isolated neutrophils were stimulated with N-formyl-methionyl-leucyl-phenylalanine (fMLP) and phorbol 12-myristate 13-acetate (PMA) and the rate of superoxide generation and elastase activity measured and compared with neutrophils from healthy age-matched controls. Neutrophils from CF patients spontaneously generated higher levels of superoxide after resolution of the exacerbation compared to control neutrophils. The stimulated generation of superoxide from control neutrophils was not significantly different from neutrophils isolated from CF patients either before or after resolution of the CF exacerbation. Neutrophils from CF patients spontaneously released more elastase than control neutrophils but released less elastase than control neutrophils in response to fMLP. The stimulated release of elastase from neutrophils was not significantly different before compared to after resolution of the exacerbation. Neutrophils from CF patients displayed a different pattern of response than those from control subjects; however, CF exacerbations did not appear to modulate neutrophil function. D

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Section: Discussionmentioning

confidence: 99%

Effect of cystic fibrosis exacerbations on neutrophil function

Brockbank

Downey

Elborn

et al. 2005

International Immunopharmacology

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“…This problem, along with recurrent airway infections and increased neutrophil activity, mean that CF patients endure regular bouts of increased oxidative stress [15]. Moreover, as both lung function and antioxidants status decline with age in CF patients [16], it is possible that these two events are linked, although no long-term prospective studies have yet addressed this interesting possibility. Encouragingly, short-term intervention studies have shown that b-carotene supplementation reduces circulating markers of lipid peroxidation in CF patients [17,18].…”

Section: The Lung and Dietary Antioxidantsmentioning

confidence: 99%

Air pollution and the elderly: oxidant/antioxidant issues worth consideration

Kelly¹,

Dunster²,

Mudway³

2003

Eur Respir J

110

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The elderly are frequently classified as being particularly susceptible to air pollution. The basis of this increased sensitivity is not known but it is likely that it is linked to age-related impaired function of the lung. However, given this uncertainty and increased impact of air pollution of this section of the community there is a need to explore the mechanisms involved.Gaseous air pollutants such as ozone and nitrogen dioxide, or many of the components adsorbed onto the surface of respirable particles, are either powerful oxidants or capable of generating free radicals. If unabated, oxidants can cause injury to the delicate cells that line the respiratory tract. Small molecular weight antioxidant defences present in respiratory tract lining fluid (RTLF) represent the first line of defence against a range of oxidants that enter the lung. The quantity and quality of the RTLF airways antioxidant network are, therefore, likely to be important determinants of the impact of the oxidant challenge on the underlying respiratory epithelium.As yet, comprehensive information on the distribution and variability of respiratory tract lining fluid antioxidant defences is only available in young, mainly healthy volunteers. Studies undertaken in patients with a range of respiratory diseases suggest that marked changes in the distribution of respiratory tract lining fluid antioxidants can occur. Information is not currently available on the impact of ageing on the respiratory tract lining fluid antioxidant defence network. As several respiratory tract lining fluid antioxidants are of dietary origin, the elderly, who often have different dietary patterns to younger individuals, may have decreased availability of important antioxidants. Given these possibilities, a better understanding of respiratory tract lining fluid antioxidant defences in the aged lung is warranted.

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“…Respiratory problems in CF arise from inhibited mucociliary clearance in the airways, exacerbated inflammation and persistent airway infection that leads to progressive damage of the lung tissue, due in part to oxidative stress (31). This notion has generated interest in the use of Se supplementation to mitigate the oxidative stress in the lungs of patients with CF.…”

Section: F Cystic Fibrosismentioning

confidence: 99%

The Role of Selenium in Inflammation and Immunity: From Molecular Mechanisms to Therapeutic Opportunities

Huang

Rose

Hoffmann

2012

Antioxidants & Redox Signaling

715

496

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Dietary selenium (]Se), mainly through its incorporation into selenoproteins, plays an important role in inflammation and immunity. Adequate levels of Se are important for initiating immunity, but they are also involved in regulating excessive immune responses and chronic inflammation. Evidence has emerged regarding roles for individual selenoproteins in regulating inflammation and immunity, and this has provided important insight into mechanisms by which Se influences these processes. Se deficiency has long been recognized to negatively impact immune cells during activation, differentiation, and proliferation. This is related to increased oxidative stress, but additional functions such as protein folding and calcium flux may also be impaired in immune cells under Se deficient conditions. Supplementing diets with above-adequate levels of Se can also impinge on immune cell function, with some types of inflammation and immunity particularly affected and sexually dimorphic effects of Se levels in some cases. In this comprehensivearticle, the roles of Se and individual selenoproteins in regulating immune cell signaling and function are discussed. Particular emphasis is given to how Se and selenoproteins are linked to redox signaling, oxidative burst, calcium flux, and the subsequent effector functions of immune cells. Data obtained from cell culture and animal models are reviewed and compared with those involving human physiology and pathophysiology, including the effects of Se levels on inflammatory or immune-related diseases including anti-viral immunity, autoimmunity, sepsis, allergic asthma, and chronic inflammatory disorders. Finally, the benefits and potential adverse effects of intervention with Se supplementation for various inflammatory or immune disorders are discussed. Antioxid. Redox Signal. 16, 705-743.

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Pulmonary dysfunction in cystic fibrosis is associated with oxidative stress

Cited by 148 publications

References 30 publications

Effect of cystic fibrosis exacerbations on neutrophil function

Effect of cystic fibrosis exacerbations on neutrophil function

Air pollution and the elderly: oxidant/antioxidant issues worth consideration

The Role of Selenium in Inflammation and Immunity: From Molecular Mechanisms to Therapeutic Opportunities

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