Cystic fibrosis F508del patients have apically localized CFTR in a reduced number of airway cells

Lab Invest. 2000 Jun;80(6):857-68. doi: 10.1038/labinvest.3780090.


Present state of knowledge, mostly based on heterologous expression studies, indicates that the cystic fibrosis transmembrane conductance regulator (CFTR) protein bearing the F508del mutation is misprocessed and mislocalized in the cytoplasm, unable to reach the cell surface. Recently, however, it was described that protein levels and localization are similar between F508del and wild-type CFTR in airway and intestinal tissues, but not in the sweat glands. In this study, we used immunocytochemistry with three different anti-CFTR antibodies to investigate endogenous CFTR expression and localization in nasal epithelial cells from F508del homozygous patients, F508del carriers, and non-CF individuals. On average, 300 cells were observed per individual. No significant differences were observed for cell type distributions among CF, carrier, and non-CF samples; epithelial cells made up approximately 80% to 95% of all cells present. CFTR was detected mostly in the apical region (AR) of the tall columnar epithelial (TCE) cells, ciliated or nonciliated. By confocal microscopy analysis, we show that the CFTR apical region-staining does not overlap with either anti-calnexin (endoplasmic reticulum), anti-p58 (Golgi), or anti-tubulin (cilia) stainings. The median from results with three antibodies indicate that the apical localization of CFTR happens in 22% of TCE cells from F508del homozygous patients with CF (n = 12), in 42% of cells from F508del carriers (n = 20), and in 56% of cells from healthy individuals (n = 12). Statistical analysis indicates that differences are significant among all groups studied and for the three antibodies (p < 0.05). These results confirm the presence of CFTR in the apical region of airway cells from F508del homozygous patients; however, they also reveal that the number of cells in which this occurs is significantly lower than in F508del carriers and much lower than in healthy individuals. These findings may have an impact on the design of novel pharmacological strategies aimed at circumventing the CF defect caused by the F508del mutation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cystic Fibrosis / genetics*
  • Cystic Fibrosis / pathology*
  • Cystic Fibrosis Transmembrane Conductance Regulator / analysis
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • Genetic Carrier Screening
  • Humans
  • Immunohistochemistry
  • Intestinal Mucosa / pathology
  • Nasal Mucosa / cytology
  • Nasal Mucosa / pathology*
  • Organ Specificity
  • Reference Values
  • Sequence Deletion*
  • Sweat Glands / pathology


  • CFTR protein, human
  • Cystic Fibrosis Transmembrane Conductance Regulator