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

TY - JOUR

T1 - Cyanide levels found in infected cystic fibrosis sputum inhibit airway ciliary function

AU - Nair, Chandrika

AU - Shoemark, Amelia

AU - Chan, Mario

AU - Ollosson, Sarah

AU - Dixon, Mellissa

AU - Hogg, Claire

AU - Alton, Eric W.F.W.

AU - Davies, Jane C.

AU - Williams, Huw D.

N1 - Publisher Copyright: Copyright © ERS 2014.

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/84938086626

U2 - 10.1183/09031936.00097014

DO - 10.1183/09031936.00097014

M3 - Article

C2 - 25186256

AN - SCOPUS:84938086626

SN - 0903-1936

VL - 44

SP - 1253

EP - 1261

JO - European Respiratory Journal

JF - European Respiratory Journal

IS - 5

ER -