The importance of CFTR expression for neutrophil function in patients with Cystic Fibrosis

Abstract

Background Cystic fibrosis (CF) is a genetic disease characterised by chronic bacterial infection of the lung and destruction of lung tissue eventually leading to respiratory failure. CF is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. Current treatment focuses on managing the symptoms of CF including antibiotic therapy against respiratory infections and vitamin and enzyme supplements to treat pancreatic insufficiency. However, a new drug known as ivacaftor has been approved recently that treats the underlying defect and corrects the defective CFTR in carriers of the G551D mutation. Neutrophils in CF fail to eradicate pathogens causing lung infections. Reports suggesting dysregulated neutrophil activity in CF illustrated altered gene expression and increased release of proteases from primary granules. However, it remains unknown whether neutrophil dysfunction is due to chronic inflammation or the CFTR defect. Our hypothesis is that impaired neutrophil activity in CF is directly caused by a lack of CFTR protein and function. Therefore, the aim of this study was to examine CFTR expression in neutrophils by optimising the methods for optimal CFTR protein detection, by comparing the levels of expression of mature CFTR protein in healthy control and CF neutrophils to epithelial cells and by examining the function of the CFTR channel in neutrophils.