Goldman M J, Anderson G M, Stolzenberg E D, Kari U P, Zasloff M, Wilson J M
Department of Medicine, The University of Pennsylvania Medical Center, Philadelphia 19104, USA.
Cell. 1997 Feb 21;88(4):553-60. doi: 10.1016/s0092-8674(00)81895-4.
A human bronchial xenograft model was used to characterize the molecular basis for the previously described defect in bacterial killing that is present in the cystic fibrosis (CF) lung. Airway surface fluid from CF grafts contained abnormally high NaCl and failed to kill bacteria, defects that were corrected with adenoviral vectors. A full-length clone for the only known human beta-defensin (i.e., hBD-1) was isolated. This gene is expressed throughout the respiratory epithelia of non-CF and CF lungs, and its protein product shows salt-dependent antimicrobial activity to P. aeruginosa. Antisense oligonucleotides to hBD-1 ablated the antimicrobial activity in airway surface fluid from non-CF grafts. These data suggest that hBD-1 plays an important role in innate immunity that is compromised in CF by its salt-dependent inactivation.
使用人支气管异种移植模型来表征先前描述的囊性纤维化（CF）肺中存在的细菌杀伤缺陷的分子基础。CF移植物的气道表面液体含有异常高的氯化钠且无法杀死细菌，这些缺陷可通过腺病毒载体得到纠正。分离出了唯一已知的人β-防御素（即hBD-1）的全长克隆。该基因在非CF和CF肺的整个呼吸道上皮中表达，其蛋白质产物对铜绿假单胞菌具有盐依赖性抗菌活性。针对hBD-1的反义寡核苷酸消除了非CF移植物气道表面液体中的抗菌活性。这些数据表明，hBD-1在先天性免疫中起重要作用，在CF中由于其盐依赖性失活而受损。
