Functional properties of mixed cystic fibrosis and normal bronchial epithelial cell cultures.
Cystic fibrosis (CF) airway epithelia exhibit altered Cl(-) and Na(+) transport properties and increased IL-8 secretion. In the present study, we examined whether a small proportion of cells with a normal phenotype could normalize the ion transport and IL-8 secretion properties of a CF airway epithelial cell layer. We obtained three types of primary cultures of human bronchial epithelial cells: one composed of 100% non-CF cells, one of 100% CF cells, and one of 10% non-CF and 90% CF cells ("cocultures"). Measurement of the bioelectric properties in Ussing chambers revealed that the cocultures displayed Cl(-) and Na(+) transports similar to those observed in the 100% non-CF cultures and significantly different from CF cultures. IL-8 concentration in the coculture supernatant was not different from non-CF cultures, but was significantly lower than in CF cultures. This study provides evidence that 10% bronchial epithelial cells expressing a normal phenotype are sufficient to functionally correct a primary culture of CF bronchial epithelial cells in vitro. We postulate that 10% cells with a non-CF phenotype can be used as a goal for the design of gene therapy and cell therapy trials for CF lung disease.
Dannhoffer
Luc
L
Université de Versailles Saint Quentin en Yvelines, UPRES EA 220, Laboratoire de Biologie et Pharmacologie des Epithéliums Respiratoires, UFR Paris Ile de France Ouest, Boulogne, France.
Blouquit-Laye
Sabine
S
Regnier
Agathe
A
Chinet
Thierry
T
D000328:Adult; D017209:Apoptosis; D001982:Bronchial Diseases / Q000378:metabolism; D049109:Cell Proliferation; D018920:Coculture Techniques; D003550:Cystic Fibrosis / Q000378:metabolism* / Q000473:pathology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D030342:Genetic Diseases, Inborn / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods; D006720:Homozygote; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D007477:Ions; D008297:Male; D010641:Phenotype
D016209:Interleukin-8; D007477:Ions