REGIONAL ION TRANSPORT ACROSS AIRWAY EPITHELIUM

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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.