Fas and Fas ligand expression in cystic fibrosis airway epithelium

Background-Cystic fibrosis (CF) is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and de fective expression of CFTR protein in epithelial cells. The main cause of m ortality in CF is Linked to chronic inflammatory and infectious airway proc esses. Recent studies have suggested perturbations in the apoptotic process in CF cell lines and enterocytes. A study was undertaken to investigate th e expression of Fas and Fas ligand (Fast) in CF bronchial epithelium and CF tracheal cell lines. Methods-Immunohistochemical staining for Fas (alkaline phosphatase anti-alk aline phosphatase) and Fast (immunoperoxidase) was performed in eight CF br onchial epithelial samples and four controls and immunohistochemical DNA fr agmentation (TUNEL) was carried out in four CF patients and four controls. Immunofluorescence staining and flow cytometric analysis of Fas and Fast ex pression was performed in two human tracheal epithelial cell lines (HTEC) w ith normal and CF genotype. The dosage of serum soluble Fast was examined i n 21 patients with CF and 14 healthy volunteers. Results-Fast expression was markedly increased in patients with CF in both the ciliated and submucosal glandular bronchial epithelium compared with co ntrols; Fas was similarly expressed in bronchial samples from controls and CF patients in both the ciliated epithelium and submucosal glands. High lev els of DNA fragmentation were observed in CF but with some epithelial cell alterations. Serum concentrations of soluble Fast were frequently undetecta ble in patients with CE In vitro, HTEC expressed Fas and Fast in both genot ypes. A higher mean fluorescence intensity for Fast expression was noted in CF genotype HTEC with median (range) for six experiments of 74 (25-101) fo r CF cells and 42 (21-70) for non-CF cells. Conclusion-Fas/FasL interaction is probably implicated in the human CF airw ay apoptotic pathway. The mechanisms of induction of Fast expression and it s role in inducing tissue damage or remodelling or in controlling local inf lammatory cell apoptosis remain to be determined.