Birrer P, McElvaney N G, Rüdeberg A, Sommer C W, Liechti-Gallati S, Kraemer R, Hubbard R, Crystal R G
Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.
Am J Respir Crit Care Med. 1994 Jul;150(1):207-13. doi: 10.1164/ajrccm.150.1.7912987.
Cystic fibrosis (CF) is characterized in the lung by chronic purulent bronchitis culminating in pulmonary insufficiency. There is evidence to suggest that neutrophil elastase (NE) released by neutrophils on the respiratory epithelial surface plays a major role in the pathogenesis of this lung disease. This study sought to determine the age of onset of the chronic neutrophil-dominated inflammation in CF and the consequences to the NE-anti-NE screen on the respiratory epithelial surface of the CF lung. NE and anti-NE defensive molecules were evaluated in respiratory epithelial lining fluid (ELF) in 27 children with stable CF (1 to 18 yr of age). Despite normal antigenic concentrations of alpha 1-antitrypsin (alpha 1AT) and secretory leukoprotease inhibitor (SLPI), 25 of 27 children with CF had neutrophil-dominated inflammation (> 500 neutrophils/microliters ELF). Active NE was found in ELF in 20 of 27 children, including two of four aged 1 yr. Western blot analysis showed the majority of alpha 1AT and SLPI molecules to be complexed and/or degraded. These observations demonstrate that a chronic imbalance of the NE-anti-NE protective screen develops early on the respiratory epithelial surface in persons with CF and is likely well established by 1 yr of age, with resultant potential for lung damage.
囊性纤维化（CF）在肺部的特征是慢性化脓性支气管炎，最终导致肺功能不全。有证据表明，中性粒细胞在呼吸道上皮表面释放的中性粒细胞弹性蛋白酶（NE）在这种肺部疾病的发病机制中起主要作用。本研究旨在确定CF中以中性粒细胞为主的慢性炎症的发病年龄，以及CF肺部呼吸道上皮表面NE-抗NE筛查的后果。对27名病情稳定的CF儿童（1至18岁）的呼吸道上皮衬液（ELF）中的NE和抗NE防御分子进行了评估。尽管α1-抗胰蛋白酶（α1AT）和分泌型白细胞蛋白酶抑制剂（SLPI）的抗原浓度正常，但27名CF儿童中有25名以中性粒细胞为主的炎症（>500个中性粒细胞/微升ELF）。27名儿童中有20名在ELF中发现了活性NE，其中包括4名1岁儿童中的2名。蛋白质印迹分析表明，大多数α1AT和SLPI分子被复合和/或降解。这些观察结果表明，CF患者呼吸道上皮表面早期就出现了NE-抗NE保护屏障的慢性失衡，并且很可能在1岁时就已确立，从而导致肺部损伤的可能性。
