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Cyanide levels found in infected cystic fibrosis sputum inhibit airway ciliary function

Chandrika Nair, Amelia Shoemark, Mario Chan, Sarah Ollosson, Mellissa Dixon, Claire Hogg, Eric W.F.W. Alton, Jane C. Davies, Huw D. Williams
European Respiratory Journal 2014; DOI: 10.1183/09031936.00097014
Chandrika Nair
1Dept of Life Sciences, Imperial College, London, UK
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Amelia Shoemark
2Dept of Paediatric Respiratory Medicine, Royal Brompton Hospital, London, UK
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Mario Chan
3Dept of Gene Therapy, Imperial College, London, UK
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Sarah Ollosson
2Dept of Paediatric Respiratory Medicine, Royal Brompton Hospital, London, UK
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Mellissa Dixon
2Dept of Paediatric Respiratory Medicine, Royal Brompton Hospital, London, UK
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Claire Hogg
2Dept of Paediatric Respiratory Medicine, Royal Brompton Hospital, London, UK
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Eric W.F.W. Alton
3Dept of Gene Therapy, Imperial College, London, UK
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Jane C. Davies
3Dept of Gene Therapy, Imperial College, London, UK
4Joint senior authors
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Huw D. Williams
1Dept of Life Sciences, Imperial College, London, UK
4Joint senior authors
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  • For correspondence: h.d.williams@imperial.ac.uk
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Abstract

We have previously reported cyanide at concentrations of up to 150 μM in the sputum of cystic fibrosis patients infected with Pseudomonas aeruginosa and a negative correlation with lung function. Our aim was to investigate possible mechanisms for this association, focusing on the effect of pathophysiologically relevant cyanide levels on human respiratory cell function.

Ciliary beat frequency measurements were performed on nasal brushings and nasal air–liquid interface (ALI) cultures obtained from healthy volunteers and cystic fibrosis patients.

Potassium cyanide decreased ciliary beat frequency in healthy nasal brushings (n = 6) after 60 min (150 μM: 47% fall, p<0.0012; 75 μM: 32% fall, p<0.0001). Samples from cystic fibrosis patients (n = 3) showed similar results (150 μM: 55% fall, p = 0.001). Ciliary beat frequency inhibition was not due to loss of cell viability and was reversible. The inhibitory mechanism was independent of ATP levels. KCN also significantly inhibited ciliary beat frequency in ALI cultures, albeit to a lesser extent. Ciliary beat frequency measurements on ALI cultures treated with culture supernatants from P. aeruginosa mutants defective in virulence factor production implicated cyanide as a key component inhibiting the ciliary beat frequency.

If cyanide production similarly impairs mucocilliary clearance in vivo, it could explain the link with increased disease severity observed in cystic fibrosis patients with detectable cyanide in their airway.

Abstract

Cyanide levels detectable in sputum inhibit ciliary function http://ow.ly/zK3Vy

  • Received May 27, 2014.
  • Accepted July 14, 2014.
  • ©ERS
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Cyanide levels found in infected cystic fibrosis sputum inhibit airway ciliary function
Chandrika Nair, Amelia Shoemark, Mario Chan, Sarah Ollosson, Mellissa Dixon, Claire Hogg, Eric W.F.W. Alton, Jane C. Davies, Huw D. Williams
European Respiratory Journal Jan 2014, erj00970-2014; DOI: 10.1183/09031936.00097014

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Cyanide levels found in infected cystic fibrosis sputum inhibit airway ciliary function
Chandrika Nair, Amelia Shoemark, Mario Chan, Sarah Ollosson, Mellissa Dixon, Claire Hogg, Eric W.F.W. Alton, Jane C. Davies, Huw D. Williams
European Respiratory Journal Jan 2014, erj00970-2014; DOI: 10.1183/09031936.00097014
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