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Departments of Anatomy and Cell Biology and of Internal Medicine, University of Iowa Medical School, Iowa City, Iowa 52242
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 µl/cm2;
n = 17) was significantly less than
that of non-CF xenografts (35 ± 2.4 µl/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 (~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.
ion transport; electrolyte and water balance; lung epithelium; salt absorption
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