Airway surface fluid volume and Cl content in cystic fibrosis and normal bronchial xenografts

We describe theuse of an in vivo human bronchial xenograft model of cystic fibrosis(CF) and non-CF airways to investigate pathophysiological alterationsin airway surface fluid (ASF) volume (V_s) and Cl content.V_s was calculated based on thedilution of an impermeable marker,[³H]inulin, duringharvesting of ASF from xenografts with an isosmotic Cl-free solution.These calculations demonstrated thatV_s in CF xenographs (28 ± 3.0 µl/cm²;n = 17) was significantly less thanthat of non-CF xenografts (35 ± 2.4 µl/cm²;n = 30). The Cl concentration of ASF([Cl]_s) wasdetermined using a solid-state AgCl electrode and adjusted for dilutionduring harvesting using the impermeable[³H]inulin marker.Cumulative results demonstrate small but significant elevations(P < 0.045) in[Cl]_s in CF (125 ± 4 mM; n = 27) compared with non-CF(114 ± 4 mM; n = 48) xenografts.To investigate potential mechanisms by which CF airways may facilitatea higher level of fluid absorption yet retain slightly elevated levelsof Cl, we sought to evaluate the capacity of CF and non-CF airways toabsorb both ²²Na and³⁶Cl. Two consistent findings wereevident from these studies. First, in both CF and non-CF xenografts,²²Na and³⁶Cl were always absorbed in anequal molar ratio. Second, CF xenografts hyperabsorbed (~1.5-foldhigher) both ²²Na and³⁶Cl compared with non-CFxenografts. These results substantiate previously documented findingsof elevated Na absorption in CF airways and also suggest that theslightly elevated[Cl]_s found in thisstudy of CF xenograft epithelia does not occur through a mechanism ofdecreased apical permeability to Cl.