Journal
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
Volume 290, Issue 3, Pages C741-C749Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpcell.00379.2005
Keywords
cystic fibrosis transmembrane conductance regulator; airway; fluorescence microscopy; pH regulation
Categories
Funding
- NEI NIH HHS [EY-13574] Funding Source: Medline
- NHLBI NIH HHS [HL-73856, HL-59198] Funding Source: Medline
- NIBIB NIH HHS [EB-00415] Funding Source: Medline
- NIDDK NIH HHS [DK-35124, DK-72517] Funding Source: Medline
Ask authors/readers for more resources
Prior studies have shown that fluid secretions from airway submucosal glands in cystic fibrosis (CF) are reduced and hyperviscous, possibly contributing to the pathogenesis of CF airway disease. Because the CF transmembrane conductance regulator (CFTR) protein can transport both chloride and bicarbonate, we investigated whether gland fluid pH is abnormal in early CF, using nasal biopsies from pediatric subjects having minimal CF lung disease. Gland fluid pH, measured in freshly secreted droplets under oil stained with BCECF-dextran, was 6.57 +/- 0.09 ( mean +/- SE) in biopsies from six CF subjects, significantly lower than 7.18 +/- 0.06 in eight non-CF biopsies (P < 0.01). To rule out the possibility that the apparent gland fluid hyperacidity in CF results from modification of fluid pH by the airway surface, a microcannulation method was used to measure pH in fluid exiting gland orifices. In pig trachea and human bronchi, gland fluid pH was reduced by up to 0.45 units by CFTR inhibitors, but was not affected by amiloride. Acid base transport in the surface epithelium of pig trachea was studied from pH changes in 300-nl fluid droplets deposited onto the oil-covered airway surface. The droplets had specified ionic composition/pH and/or contained transporter activators/inhibitors. We found evidence for CFTR-dependent bicarbonate transport by the tracheal surface epithelium as well as ATP/histamine-stimulated proton secretion, but not for sodium/proton or chloride/bicarbonate exchange. These results provide evidence for intrinsic hyperacidity in CF gland fluid secretions, which may contribute to CF airway pathology.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available