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 (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

We have previously reported cyanide at concentrations of up to 150 mM 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 (n56) after 60 min (150 mM: 47% fall, p,0.0012; 75 mM: 32% fall, p,0.0001). Samples from cystic fibrosis patients (n53) showed similar results (150 mM: 55% fall, p50.001). 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.

Original languageEnglish
Pages (from-to)1253-1261
Number of pages9
JournalEuropean Respiratory Journal
Volume44
Issue number5
Early online date31 Oct 2014
DOIs
Publication statusPublished - 2014

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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