In vitro expression of Fas and CD40 and induction of apoptosis in human cystic fibrosis airway epithelial cells

Abstract

Cystic fibrosis is characterized by a damaged airway epithelium with inflammation and chronic infection. The aim of this study was to investigate the process of apoptosis in this disease. To evaluate the effects of interferonγ and the Fas apoptotic pathway on cystic fibrosis airway epithelial cells, we used immortalized cystic fibrosis (CFT-1 and CFT-2) and normal (NT-1) human tracheal epithelial cell lines. Cell death was determined using annexin-V/propidium iodide labelling and electron microscopy. In vitro expression of Fas and CD40 surface antigens was analysed by immunofluorescence staining and flow cytometry. Normal and cystic fibrosis cells constitutively express these antigens. CD40, but not Fas expression, was upregulated by interferon γ. Treatment of interferon γ -stimulated cells with anti-Fas resulted in apoptosis for about 80% of CFT-2 (homozygous for Δ F508 deletion) cells and for 35–40% of CFT-1 (heterozygous) or normal cells. Our results suggest that Fas may mediate apoptosis in cystic fibrosis airway epithelium.