Osmotic water permeabilities of cultured, well-differentiated normal and cystic fibrosis airway epithelia

Current hypotheses describing the function of normal airway surface liquid (ASL) in lung defense are divergent One theory predicts that normal airways regulate ASL volume by modulating the flow of isosmotic fluid across the e pithelium, whereas an alternative theory predicts that ASL is normally hypo smotic. These hypotheses predict different values for the osmotic water per meability (P-f) of airway epithelia. We measured P-f of cultures of normal and cystic fibrosis (CF) airway epithelia that, like the native tissue, con tain columnar cells facing the lumen and basal cells that face a basement m embrane. Xz laser scanning confocal microscopy recorded changes in epitheli al height and transepithelial volume flow in response to anisosmotic challe nges. With luminal hyperosmotic challenges, transepithelial and apical memb rane P-f are relatively high for both normal and CF airway epithelia, consi stent with an isosmotic ASL. Simultaneous measurements of epithelial cell v olume and transepithelial water flow revealed that airway columnar epitheli al cells behave as osmometers whose volume is controlled by luminal osmolal ity, Basal cell volume did not change in these experiments. When the serosa l side of the epithelium was challenged with hyperosmotic solutions, the ba sal cells shrank, whereas the lumen-facing columnar cells did not. We concl ude that (a) normal and CF airway epithelia have relatively high water perm eabilities, consistent with the isosmotic ASL theory, and the capacity to r estore water on airway surfaces lost by evaporation, and (b) the columnar c ell basolateral membrane and tight junctions limit transepithelial water fl ow in this tissue.