Conventional theories on lung liquid balance have long embraced the notion that distal small airway epithelium secretes liquid into the airway lumen to hydrate airway surfaces and support mucociliary transport. As this lumenal liquid is swept by cilia into the large airways, where aggregate cross sectional area is much smaller, it is reasoned that liquid absorption must occur to reduce liquid volume and prevent occlusion of the airspace. Active transepithelial ion transport is thought to provide the principal driving force for this liquid movement across airway epithelia. These theories on airway liquid balance are supported by findings that accessible large airways, such as trachea and large bronchi, actively absorb ions (driven by active Na+ absorption). However, the region of the small airways where secretion of ions and liquid occur remains elusive because the complex morphology of the lung precludes study of these tissues by conventional means. Recently, techniques have been developed by this laboratory which permit dissection and cannulation of small bronchi and bronchioles (> 100 mu m lumen diameter) so that ion transport and bioelectric properties can now be assessed in vitro in both large and small airway epithelium. The central hypothesis of the present study is that differences in transepithelial ion and liquid transport exist between large and small airway epithelium. Specifically, it is hypothesized that ions and liquid are absorbed across large airway epithelium and secrets across small airway epithelium. These hypotheses will be tested in three stages: l) characterization of transepithelial bioelectric properties, 2) measurement of radioisotopic fluxes of physiologically important solutes, and 3) determination of transepithelial liquid flow. Large airways will be mounted in Ussing chambers while intermediate to small airways will be cannulated with glass or polyethylene tubing. Selective inhibitors and stimulators of sodium and chloride transport will be used to identify these specific pathways and to modulate transepithelial ion and liquid flow. Identification and characterization of active ion transport processes which are present in specific regions of the airway epithelium will greatly facilitate our understanding of the etiology and pathophysiology of important pulmonary diseases and disorders such as cystic fibrosis and pulmonary edema.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
1R29HL048622-01A4
Application #
2224692
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1995-04-01
Project End
2000-02-29
Budget Start
1995-04-01
Budget End
1996-02-29
Support Year
1
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of South Alabama
Department
Physiology
Type
Schools of Medicine
DUNS #
City
Mobile
State
AL
Country
United States
Zip Code
36688
Trout, Laura; Townsley, Mary I; Bowden, Amy L et al. (2003) Disruptive effects of anion secretion inhibitors on airway mucus morphology in isolated perfused pig lung. J Physiol 549:845-53
Ballard, Stephen T; Trout, Laura; Mehta, Anil et al. (2002) Liquid secretion inhibitors reduce mucociliary transport in glandular airways. Am J Physiol Lung Cell Mol Physiol 283:L329-35
Crews, A; Taylor, A E; Ballard, S T (2001) Liquid transport properties of porcine tracheal epithelium. J Appl Physiol 91:797-802
Trout, L; Corboz, M R; Ballard, S T (2001) Mechanism of substance P-induced liquid secretion across bronchial epithelium. Am J Physiol Lung Cell Mol Physiol 281:L639-45
Ballard, S T; Trout, L; Bebok, Z et al. (1999) CFTR involvement in chloride, bicarbonate, and liquid secretion by airway submucosal glands. Am J Physiol 277:L694-9
Trout, L; King, M; Feng, W et al. (1998) Inhibition of airway liquid secretion and its effect on the physical properties of airway mucus. Am J Physiol 274:L258-63
Inglis, S K; Corboz, M R; Ballard, S T (1998) Effect of anion secretion inhibitors on mucin content of airway submucosal gland ducts. Am J Physiol 274:L762-6
Trout, L; Gatzy, J T; Ballard, S T (1998) Acetylcholine-induced liquid secretion by bronchial epithelium: role of Cl- and HCO3- transport. Am J Physiol 275:L1095-9
Inglis, S K; Corboz, M R; Taylor, A E et al. (1997) Effect of anion transport inhibition on mucus secretion by airway submucosal glands. Am J Physiol 272:L372-7
Inglis, S K; Corboz, M R; Taylor, A E et al. (1997) In situ visualization of bronchial submucosal glands and their secretory response to acetylcholine. Am J Physiol 272:L203-10

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