The role of airway epithelium and blood neutrophils in the inflammatory response in cystic fibrosis.

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, which accounts for the cAMP-modulated chloride conductance of airway epithelial cells. CFTR also regulates other membrane proteins like the negative regulation of the amiloride-sensitive epithelial sodium channel (ENaC). Mutations in the CFTR gene lead to hyperabsorption of sodium chloride and a reduction in the periciliary salt and water content which leads to impaired mucociliary clearance. It seems that a lack of functional CFTR leads to abnormal function of the NF-kappaB pathway in submucosal gland cells, causing an increased production of pro-inflammatory cytokines and the chemokine IL-8, and a pro-inflammatory environment. CFTR is also expressed in neutrophils and several neutrophil functions like cytokine production, migration, phagocytosis and apoptosis seem altered in CF. In this review we describe the role of airway epithelium and blood neutrophils in the viscious circle of inflammation and infection seen in CF.