Bioelectric properties of human cystic fibrosis and non-cystic fibrosis fetal tracheal xenografts in SCID mice
Tirouvanziam, R.; Desternes, M.; Saari, A.; Puchelle, E.; Péault, B.; Chinet, T.
American Journal of Physiology 274(4): C875-C882
1998
ISSN/ISBN: 0002-9513 PMID: 9575783 Document Number: 486714
We measured the bioelectric properties of 14 cystic fibrosis (CF) and 33 non-CF human fetal tracheal xenografts in severe combined immunodeficiency (SCID) mice. All xenografts exhibited a mature airway-type epithelium irrespective of their gestational age, duration of engraftment, and genotype. The in vivo potential difference and the in vitro baseline short-circuit current (Isc) were significantly higher in non-CF than in CF xenografts. In non-CF xenografts, sequential addition of amiloride, forskolin, and ATP resulted in a 39.4% decrease, a 24.1% increase, and a 43.6% increase in Isc, respectively. In CF xenografts, forskolin had no significant effect on Isc, whereas amiloride- and ATP-induced changes in Isc were proportionally higher than in non-CF xenografts (-60.0 and + 68.8%, respectively). These results indicate that the bioelectric properties of non-CF xenografts are similar to those of postnatal airways and that CF xenografts exhibit lower baseline electrogenic activity than non-CF xenografts but similar regulation of ion transport processes to postnatal CF airways. This model of mature human fetal tracheal mucosa may help gain insight into early CF airway pathogenesis.