Effect of cystic fibrosis exacerbations on neutrophil function

Brockbank, Simon; Downey, D.G.; Elborn, J. Stuart; Ennis, Madeleine

doi:10.1016/j.intimp.2004.11.007

Cited by 25 publications

(21 citation statements)

References 28 publications

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“…Serum levels of S100A12 [34], S100A8/A9, CRP and vascular endothelial growth factor [35] have also been suggested as serum markers of acute infectious exacerbations and to decrease significantly post treatment of an exacerbation. Moreover, while CF exacerbations were not shown to modulate neutrophil function [36], neutrophil derived proteins including myeloperoxidase in peripheral blood appeared to reflect inflammatory changes post antibiotic treatment [37]. Myeloperoxidase however is a component of neutrophil primary/azurophilic granules and peroxidase exocytosis is a tightly regulated process.…”

Section: Discussionmentioning

confidence: 99%

A novel neutrophil derived inflammatory biomarker of pulmonary exacerbation in cystic fibrosis

Reeves

Bergin

Fitzgerald

et al. 2012

Journal of Cystic Fibrosis

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Section: Discussionmentioning

confidence: 99%

A novel neutrophil derived inflammatory biomarker of pulmonary exacerbation in cystic fibrosis

Reeves

Bergin

Fitzgerald

et al. 2012

Journal of Cystic Fibrosis

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“…This may partly explain why P. aeruginosa rapidly becomes the predominant pathogen in CF, apparently displacing other bacterial species. Secondly, cyanide will be directly toxic to airway cells and, finally, cyanide may also contribute to the relative inability of neutrophils to clear P. aeruginosa infection in the CF lung [15,16]. In the concentrations reported, cyanide has been shown to inhibit the function of the enzyme myeloperoxidase and prevent production of hypochlorous acid during the oxidative burst [17].…”

Section: Discussionmentioning

confidence: 99%

Bacterial cyanogenesis occurs in the cystic fibrosis lung

Sanderson¹,

Wescombe²,

Kirov³

et al. 2008

Eur Respir J

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The cystic fibrosis (CF) lung environment is poorly defined, but data suggest that bacteria may encounter reduced oxygen tensions and possibly an anaerobic environment. Pseudomonas aeruginosa produces the potent toxin cyanide under strictly microaerobic conditions. Evidence of bacterial cyanogenesis in the CF lung was investigated in the present study by measuring sputum cyanide concentrations.Sputum cyanide was measured in seven stable CF patients, as well as before and after intravenous antibiotic therapy during a hospital admission in a further eight patients experiencing acute exacerbations. All patients were chronically infected with P. aeruginosa. Comparative sputum data were obtained from nine CF patients with no documented P. aeruginosa infection and 10 healthy, nonsmoking normal controls.High levels of cyanide were detected in all the P. aeruginosa-infected stable CF patients (median (range) 0.56 (0.37-2.81) mg?mL -1 ), and in seven out of eight acute sputum samples (0.73 (0-1.43) mg?mL -1 ). In contrast, cyanide was not detectable in sputum from eight out of nine CF patients without P. aeruginosa infection or in any of the normal controls. Intravenous antibiotic treatment significantly reduced sputum cyanide levels (median 0.73 to median 0.0 mg?mL -1 ).The cyanide detected indicates that the cystic fibrosis lung provides a predominantly microaerobic environment for Pseudomonas aeruginosa. Cyanide is likely to be a potentially important virulence factor in Pseudomonas aeruginosa-infected cystic fibrosis patients.

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“…Most studies addressing the mechanisms of CF airway disease pathogenesis have focused on epithelial cells and neutrophils (4,(45)(46)(47)(48)(49)(50). These cell types are important contributors to the altered airway environment.…”

Section: Discussionmentioning

confidence: 99%

Aspergillus fumigatus Generates an Enhanced Th2-Biased Immune Response in Mice with Defective Cystic Fibrosis Transmembrane Conductance Regulator

Allard

Poynter

Marr

et al. 2006

The Journal of Immunology

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Cystic fibrosis (CF) lung disease is characterized by persistent airway inflammation and airway infection that ultimately leads to respiratory failure. Aspergillus sp. are present in the airways of 20–40% of CF patients and are of unclear clinical significance. In this study, we demonstrate that CF transmembrane conductance regulator (CFTR)-deficient (CFTR knockout, Cftrtm1Unc-TgN(fatty acid-binding protein)CFTR) and mutant (ΔF508) mice develop profound lung inflammation in response to Aspergillus fumigatus hyphal Ag exposure. CFTR-deficient mice also develop an enhanced Th2 inflammatory response to A. fumigatus, characterized by elevated IL-4 in the lung and IgE and IgG1 in serum. In contrast, CFTR deficiency does not promote a Th1 immune response. Furthermore, we demonstrate that CD4+ T cells from naive CFTR-deficient mice produce higher levels of IL-4 in response to TCR ligation than wild-type CD4+ T cells. The Th2 bias of CD4+ T cells in the absence of functional CFTR correlates with elevated nuclear levels of NFAT. Thus, CFTR is important to maintain the Th1/Th2 balance in CD4+ T cells.

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Effect of cystic fibrosis exacerbations on neutrophil function

Cited by 25 publications

References 28 publications

A novel neutrophil derived inflammatory biomarker of pulmonary exacerbation in cystic fibrosis

A novel neutrophil derived inflammatory biomarker of pulmonary exacerbation in cystic fibrosis

Bacterial cyanogenesis occurs in the cystic fibrosis lung

Aspergillus fumigatus Generates an Enhanced Th2-Biased Immune Response in Mice with Defective Cystic Fibrosis Transmembrane Conductance Regulator

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