Localisation of wild-type and Delta F508-CFTR in nasal epithelial cells

Wild-type and the Delta F508 mutation of the cystic fibrosis transmembrane conductance regulator (Delta F508-CFTR) were localised by confocal imaging in Delta F508/Delta F508 native airway epithelial cells using a well-charac terised CFTR antibody. Surface nasal epithelial cells from three control an d three CF individuals were obtained from nasal brushings. Cells were fixed , permeabilised and incubated with first antibody for 18 h at 4 degreesC. F ollowing labelling with second antibody, cells were viewed with the confoca l microscope. Wild-type CFTR was localised predominantly apically, whereas Delta F508-CFTR was located mainly inside the cell in a region close to the nucleus. Incubation of cells with MPB-07 (250 muM) at 37 degreesC for 2 h resulted in pronounced movement of Delta F508-CFTR to the cell periphery, b ut did not change the localisation of wild-type CFTR. The results show that Delta F508-CFTR is mislocalised in native nasal epithelial cells and that its distribution is altered in response to the new CFTR activator, MPB-07 T he findings should lead to development of a rational drug treatment for CF patients carrying the Delta F508 mutation.