title: Decreased expression of the cystic fibrosis transmembrane conductance regulator protein in remodeled airway epithelium from lung transplanted patients.
abstract: The absence or mislocalization of cystic fibrosis transmembrane conductance regulator (CFTR) is regarded as being specific for cystic fibrosis (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. Immunolocalization of CFTR and of epithelial differentiation markers (ie, 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 after lung transplantation. Biopsy specimens from seven non-CF and four CF patients presented either a pseudostratified respiratory epithelium or slight basal cell hyperplasia. CFTR was distributed at the apical membrane of the ciliated cells. In remodeled epithelia with basal cell hyperplasia 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 with an impairment of lung function. The results suggest that posttransplant airway epithelium dedifferentiation of the graft leads to the loss of properly targeted CFTR irrespective of the underlying disease of the recipient.
authors.affiliation: Klinische Forschergruppe, and the Department of Pneumology, Medizinische Hochschule, Hannover, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Brézillon
authors.forename: H
authors.initials: H
authors.lastname: Hamm
authors.forename: M
authors.initials: M
authors.lastname: Heilmann
authors.forename: H J
authors.initials: HJ
authors.lastname: Schäfers
authors.forename: J
authors.initials: J
authors.lastname: Hinnrasky
authors.forename: T O
authors.initials: TO
authors.lastname: Wagner
authors.forename: E
authors.initials: E
authors.lastname: Puchelle
authors.forename: B
authors.initials: B
authors.lastname: Tümmler
mesh_terms: D000328:Adult; D000367:Age Factors; D001706:Biopsy; D002454:Cell Differentiation; D003550:Cystic Fibrosis / Q000378:metabolism* / Q000473:pathology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D051180:Desmoplakins; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005541:Forced Expiratory Volume; D006801:Humans; D007633:Keratins / Q000378:metabolism; D008168:Lung / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016040:Lung Transplantation / Q000502:physiology; D008297:Male; D008875:Middle Aged
chemical_list: C505032:CFTR protein, human; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D007633:Keratins