Published ahead of print on February 11, 2005, doi:10.1164/rccm.200406-740OC Am. J. Respir. Crit. Care Med., Volume 171, Number 9, May 2005, 1026-1031 A more recent version of this article appeared on May 1, 2005
Submitted on June 21, 2004 Chloride Transport in Nasal Ciliated Cells of Cystic Fibrosis HeterozygotesIsabelle Sermet-Gaudelus1,1 Service de Pediatrie Generale, Hopital Necker-Enfants Malades, Paris, France; Faculte de Medecine Necker, INSERM U 467, Paris, France, 2 Faculte de Medecine Necker, INSERM U 467, Paris, France; MaladesLaboratoire d'Explorations Fonctionnelles Renales, Hopital Necker-Enfants Malades, Paris, France, 3 Faculte de Medecine Necker, INSERM U 467, Paris, France, 4 Service d'Histologie-Biologie Tumorale, Hopital Tenon, Paris, France, 5 Service de Biochimie-Genetique, Hopital Henri Mondor, Creteil, France, 6 Service de Biochimie, Hopital Necker-Enfants Malades, Paris, France, 7 Service d'ORL, Hopital Necker-Enfants Malades, Paris, France, 8 Centre d'Investigation Clinique, Hopital Necker-Enfants Malades, Paris, France, 9 Service de Pediatrie Generale, Hopital Necker-Enfants Malades, Paris, France * To whom correspondence should be addressed. E-mail: edelman{at}necker.fr.
Studying subjects heterozygous for mutations of the cystic fibrosis (CF) gene may help clarify the impact on disease onset of the CF transmembrane conductance regulator protein (CFTR) dependent chloride secretion. CFTR-mediated chloride transport was evaluated in 52 heterozygotes, 32 healthy controls and 77 CF patients with class I or II mutations. We measured the change in nasal potential difference in response to chloride-free isoproterenol solution for each subject and used a videoimaging fluorescent dye assay to assess the percentage of nasal ciliated cells with cAMP-dependent anion conductance. Our findings did not confirm the standard assumption that heterozygosity implies 50% of normal CFTR function. Half the heterozygotes had CFTR-mediated chloride transport levels below 50% of the normal range, and one third had levels similar to those of the CF patients. This reduced CFTR function was not associated with an elevated prevalence of CF-like symptoms in heterozygotes but was highly related to respiratory status in the CF patients. These data suggest that CFTR-dependent chloride conductance does not directly modulate disease severity but may be part of a more global defect in CF patients involving other CTFR functions or currently unknown modulatory factors. Key words: Cystic fibrosis, heterozygotes, nasal potential difference, CFTR,
This article has been cited by other articles:
|
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
