DECREASED EXPRESSION OF THE CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCEREGULATOR PROTEIN IN REMODELED AIRWAY EPITHELIUM FROM LUNG TRANSPLANTED PATIENTS

The absence or mislocalization of cystic fibrosis transmembrane conduc tance regulator (CFTR) is regarded as being specific for cystic fibros is (CF). In principle, the supply of a non-CF lung transplant to a CF patient should bring up normal CFTR expression in the lower airways. I mmunolocalization of CFTR and of epithelial differentiation markers ti e, cytokeratins 13, 14, and 18, and desmoplakins 1 and 2) was carried out on 21 mucosal biopsies from the upper lobe of grafts in non-CF (n = 12) and CF patients (n = 9) retrieved between days 23 and 1,608 afte r lung transplantation. Biopsy specimens from seven non-CF and four CF patients presented either a pseudostratified respiratory epithelium o r slight basal cell hyperplasia. CFTR was distributed at the apical me mbrane of the ciliated cells. In remodeled epithelia with basal cell h yperplasia or squamous metaplasia, CFTR was either weakly expressed in the cytoplasm of the superficial epithelial cells or was undetectable . The extent of epithelium remodeling was significantly correlated wit h an impairment of lung function. The results suggest that posttranspl ant airway epithelium dedifferentiation of the graft leads to the loss of properly targeted CFTR irrespective of the underlying disease of t he recipient. (C) 1997 by W.B. Saunders Company.