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. 1999 Feb;276(2):C469-76.
doi: 10.1152/ajpcell.1999.276.2.C469.

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

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

Y Zhang et al. Am J Physiol. 1999 Feb.

Abstract

We describe the use of an in vivo human bronchial xenograft model of cystic fibrosis (CF) and non-CF airways to investigate pathophysiological alterations in airway surface fluid (ASF) volume (Vs) and Cl content. Vs was calculated based on the dilution of an impermeable marker, [3H]inulin, during harvesting of ASF from xenografts with an isosmotic Cl-free solution. These calculations demonstrated that Vs in CF xenographs (28 +/- 3.0 microliter/cm2; n = 17) was significantly less than that of non-CF xenografts (35 +/- 2. 4 microliter/cm2; n = 30). The Cl concentration of ASF ([Cl]s) was determined using a solid-state AgCl electrode and adjusted for dilution during 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 facilitate a higher level of fluid absorption yet retain slightly elevated levels of Cl, we sought to evaluate the capacity of CF and non-CF airways to absorb both 22Na and 36Cl. Two consistent findings were evident from these studies. First, in both CF and non-CF xenografts, 22Na and 36Cl were always absorbed in an equal molar ratio. Second, CF xenografts hyperabsorbed ( approximately 1.5-fold higher) both 22Na and 36Cl compared with non-CF xenografts. These results substantiate previously documented findings of elevated Na absorption in CF airways and also suggest that the slightly elevated [Cl]s found in this study of CF xenograft epithelia does not occur through a mechanism of decreased apical permeability to Cl.

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