Human beta-defensin-1 is a salt-sensitive antibiotic in lung that is inactivated in cystic fibrosis
Human beta-defensin-1 is a salt-sensitive antibiotic in lung that is inactivated in cystic fibrosis
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DOI：
10.1016/s0092-8674(00)81895-4
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发表时间：
1997-02-21
期刊：
影响因子：
64.5
通讯作者：
Wilson, JM
中科院分区：
文献类型：
--
作者：
Goldman, MJ;Anderson, GM;Wilson, JM
使用人支气管异种移植模型来表征先前描述的存在于囊性纤维化（CF）肺中的细菌杀灭缺陷的分子基础。来自CF移植物的气道表面流体含有异常高的NaCl并且未能杀死细菌，这些缺陷用腺病毒载体纠正。唯一已知的人β-防御素的全长克隆（即，hBD-1）。该基因在非CF和CF肺的整个呼吸道上皮中表达，其蛋白产物对铜绿假单胞菌表现出盐依赖性抗菌活性。hBD-1的反义寡核苷酸消除了非CF移植物的气道表面液体中的抗微生物活性。这些数据表明，hBD-1在先天免疫中起着重要作用，先天免疫在CF中通过其盐依赖性失活而受损。
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.