HUMAN BETA-DEFENSIN-1 IS A SALT-SENSITIVE ANTIBIOTIC IN LUNG THAT IS INACTIVATED IN CYSTIC-FIBROSIS

A human bronchial xenograft model was used to characterize the molecul ar basis for the previously described defect in bacterial killing that is present in the cystic fibrosis (CF) lung. Airway surface fluid fro m CF grafts contained abnormally high NaCl and failed to kill bacteria , defects that were corrected with adenoviral vectors. A full-length c lone for the only known human beta-defensin (i.e., hBD-1) was isolated . This gene is expressed throughout the respiratory epithelia of non-C F and CF lungs, and its protein product shows salt-dependent antimicro bial activity to P. aeruginosa. Antisense oligonucleotides to hBD-1 ab lated the antimicrobial activity in airway surface fluid from non-CF g rafts. These data suggest that hBD-1 plays an important role in innate immunity that is compromised in CF by its salt-dependent inactivation .