In vivo analysis of fluid transport in cystic fibrosis airway
epithelia of bronchial xenografts.
Zhang, Yulong, James Yankaskas, James Wilson, and John F. Engelhardt.
Institute for Human Gene Therapy and the Department of Molecular
and Cellular Engineering, The University of Pennsylvania Medical
Center and the Wistar Institute, Philadelphia, Pennsylvania 19104;
and the 3Division of Pulmonary Diseases, University of North
Carolina, Chapel Hill, North Carolina 27514
APStracts 2:0434C, 1995.
An in vivo human bronchial xenograft model system was used to
simultaneously analyze electrolyte and fluid transport defects in
fully differentiated human CF and non-CF proximal airways. CF airways
demonstrated three discernible defects when compared to non-CF
including: 1) a lack of cAMP inducible Cl- secretion, 2) a four fold
higher basal fluid absorption rate, and 3) an altered regulation of
fluid absorption in response to amiloride stimulated changes in Na+
transport. A unique finding in this study demonstrated that treatment
of epithelia with amiloride led to a >3- fold decrease in the
rate of fluid absorption in CF tissues as contrasted to a >3
-fold increase in the rate of fluid absorption in non-CF tissues.
Furthermore, the removal of apical Na+ from amiloride treated non-CF
xenografts was capable of ablating this amiloride-induced increase in
fluid absorption. In light of the recent interactions demonstrated
between CFTR and the rat epithelial amiloride sensitive sodium
channel (rENaC) , these findings implicate additional complexities
between the Na+ conductance pathways and fluid transport in normal
and CF proximal airways. Such findings suggest that CFTR may also
regulate amiloride insensitive Na+ channels.
Received 21 June 1995; accepted in final form 9 November 1995.
APS Manuscript Number C367-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 12 December 95