Submucosal gland secretions in airways from cystic fibrosis patients have normal [Na+] and pH but elevated viscosity
- *Departments of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco, CA 94143-0521; ‡Cardiothoracic Surgery, School of Medicine Stanford University, Stanford, CA 94305; and †Cystic Fibrosis Research Laboratory, Stanford University, Stanford, CA 94305
-
Edited by Maurice B. Burg, National Institutes of Health, Bethesda, MD, and approved April 24, 2001 (received for review February 20, 2001)
Abstract
Fluid and macromolecule secretion by submucosal glands in mammalian airways is believed to be important in normal airway physiology and in the pathophysiology of cystic fibrosis (CF). An in situ fluorescence method was applied to measure the ionic composition and viscosity of freshly secreted fluid from airway glands. Fragments of human large airways obtained at the time of lung transplantation were mounted in a humidified perfusion chamber and the mucosal surface was covered by a thin layer of oil. Individual droplets of secreted fluid were microinjected with fluorescent indicators for measurement of [Na+], [Cl−], and pH by ratio imaging fluorescence microscopy and viscosity by fluorescence recovery after photobleaching. After carbachol stimulation, 0.1–0.5 μl of fluid accumulated in spherical droplets at gland orifices in ≈3–5 min. In gland fluid from normal human airways, [Na+] was 94 ± 8 mM, [Cl−] was 92 ± 12 mM, and pH was 6.97 ± 0.06 (SE, n = 7 humans, more than five glands studied per sample). Apparent fluid viscosity was 2.7 ± 0.3-fold greater than that of saline. Neither [Na+] nor pH differed in gland fluid from CF airways, but viscosity was significantly elevated by ≈2-fold compared to normal airways. These results represent the first direct measurements of ionic composition and viscosity in uncontaminated human gland secretions and indicate similar [Na+], [Cl−], and pH to that in the airway surface liquid. The elevated gland fluid viscosity in CF may be an important factor promoting bacterial colonization and airway disease.
Footnotes
-
↵ § To whom reprint requests should be addressed. E-mail: verkman{at}itsa.ucsf.edu.
-
This paper was submitted directly (Track II) to the PNAS office.
- Abbreviations:
- CF,
- cystic fibrosis;
- ASL,
- airway surface liquid;
- BCECF,
- 2′,7′-bis-(2-carboxyethyl)-5-(and-6)-carboxy fluorescein;
- CFTR,
- cystic fibrosis transmembrane conductance regulator
- Copyright © 2001, The National Academy of Sciences
