Bals R, Weiner D J, Meegalla R L, Accurso F, Wilson J M
Institute for Human Gene Therapy, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Am J Respir Cell Mol Biol. 2001 Jul;25(1):21-5. doi: 10.1165/ajrcmb.25.1.4436.
The link between the genetic defect in cystic fibrosis (CF) and the recently described breach in pulmonary host defense has focused on the role of salt and water metabolism in the airways. Using a human bronchial xenograft model we demonstrate a salt-independent abnormality in bacterial killing in CF airway surface fluid (ASF). Biochemical characterization implicates the absence or dysfunction of a molecule critical to the constitution of normal bacterial killing. Our study suggests that CF transmembrane conductance regulator (CFTR) deficiency causes a primary abnormality in the composition of ASF that leads to a salt-independent defect in host defense. Importantly, this defect is corrected by adenovirus-mediated gene transfer of CFTR.
囊性纤维化（CF）的基因缺陷与最近所描述的肺部宿主防御功能破坏之间的联系，已聚焦于气道中盐和水代谢的作用。利用人支气管异种移植模型，我们证明了CF气道表面液体（ASF）在细菌杀灭方面存在与盐无关的异常。生化特性表明，正常细菌杀灭机制所必需的一种分子缺失或功能异常。我们的研究提示，CF跨膜传导调节因子（CFTR）缺乏会导致ASF成分出现原发性异常，进而导致宿主防御功能出现与盐无关的缺陷。重要的是，通过腺病毒介导的CFTR基因转移可纠正这一缺陷。
