RNA interference against CFTR affects HL60-derived neutrophil microbicidal function

Biosynthesis of hypochlorous acid a potent antimicrobial oxidant in phagosomes is one of the chief mechanisms employed by polymorphonuclear neutrophils to combat infections This reaction catalyzed by myeloperoxidase requires chloride anion (Cl-) as a substrate Thus Cl- availability is a rate limiting factor that affects neutrophil microbicidal function Our previous research demonstrated that defective CFTR a cAMP-activated chloride channel present in cystic fibrosis (CF) patients leads to deficient chloride transport to neutrophil phagosomes and impaired bacterial killing To confirm this finding here we used RNA interference against this chloride channel to abate CFTR expression in the neutrophil-like cells derived from HL60 cells a promyelocytic leukemia cell line with dimethyl sulfoxide The resultant CFTR deficiency in the phagocytes compromised their bactericidal capability thereby recapitulating the phenotype seen in CF patient cells The results provide further evidence suggesting that CFTR plays an important role in phagocytic host defense (C) 2010 Elsevier Inc All rights reserved