Acid and base secretion in freshly excised nasal tissue from cystic fibrosis patients with ΔF508 mutation.
BACKGROUND
Cystic fibrosis (CF) is caused by a misfunctional CF transmembrane conductance regulator (CFTR) protein, which is believed to contributes to the regulation of the airway surface liquid (ASL) pH. This study investigated acid and base secretion in freshly excised human nasal tissues from CF patients homozygous for the ΔF508 mutation.


METHODS
Human nasal mucosa was collected during sinus surgery and investigated in Ussing chambers. Mucosal equilibrium pH values and rate of acid and base secretion were determined using the pH-stat technique.


RESULTS
The equilibrium pH of nasal epithelia from ΔF508 CF patients with chronic rhinosinusitis (CRS) was pH = 7.08 ± 0.09 and was significantly lower compared to nasal epithelia from CRS patients without CF (pH = 7.33 ± 0.06) and normal subjects (pH = 7.34 ± 0.08, n = 6). The rate of base secretion in CF nasal tissues was 11.8 ± 2.4 nmol · min(−1) · cm(−2), which was significantly lower than normal (57.2 ± 9.2 nmol · min(−1) · cm(−2)). The HCO3(−) secretory rate was further increased by forskolin by 16.1% in normal, but not in CF tissues.


CONCLUSIONS
Our data suggests that CF patients exhibited significantly lower base secretion by the nasal airway epithelium. It is possible that improper regulation of ASL pH in CF may negatively impact the innate host defense system.
Division of Rhinology, Department of Otolaryngology–Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.
Do-Yeon
DY
Cho
Peter H
PH
Hwang
Beate
B
Illek
Horst
H
Fischer
D000137:Acid-Base Imbalance / Q000235:genetics*; D000143:Acids / Q000378:metabolism; D000328:Adult; D000704:Analysis of Variance; D001639:Bicarbonates / Q000378:metabolism; D001826:Body Fluids / Q000737:chemistry; D016022:Case-Control Studies; D002908:Chronic Disease; D003550:Cystic Fibrosis / Q000235:genetics* / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005260:Female; D006720:Homozygote; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D009154:Mutation / Q000235:genetics*; D009297:Nasal Mucosa / Q000378:metabolism*; D011522:Protons; D012220:Rhinitis / Q000378:metabolism; D012852:Sinusitis / Q000378:metabolism
D000143:Acids; D001639:Bicarbonates; D011522:Protons; D019005:Cystic Fibrosis Transmembrane Conductance Regulator