Our laboratory studies the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) in cultures of airway epithelium. This protein acts as a Cl channel in the apical membrane of epithelia, and may have other functions. Mutations in CFTR cause cystic fibrosis, a lethal disease in which death is due to complications arising from the gradual accumulation of airway mucous secretions. Our cultures of surface and gland airway epithelium from human trachea have ultrastructures essentially identical to those of the original tissues. We have used them to show that mediator-induced secretion of Cl across both surface and gland airway epithelium is greatly reduced in cystic fibrosis. We are now testing the hypothesis that the initial build up of airway mucus in cystic fibrosis is due to reduced Cl (and therefore fluid) secretion by the glands which results in the secretion of dehydrated mucus that is inefficiently transported by the cilia of the surface epithelium.
Yamaya, M., W.E. Finkbeiner, and J.H. Widdicombe. 1991. Altered ion transport by tracheal glands in cystic fibrosis. Am. J. Physiol. 261:L491-L494.
Yamaya, M., W.E. Finkbeiner, S.Y. Chun, and J.H. Widdicombe. 1992. Differentiated structure and function of cultures from human tracheal epithelium. Am. J. Physiol. 262:L713-L724.
Jiang, C., W.E. Finkbeiner, J.H. Widdicombe, P.B. McCray, and S.S. Miller. 1993. Altered fluid transport across airway epithelium in cystic fibrosis. Science. 262: 424-427.
Finkbeiner, W.E., B-Q. Shen, and J.H. Widdicombe. 1994. Chloride secretion and function of serous and mucous cells of human airway glands. Am. J. Physiol. 267:L206-L210.