PROTEASE-ANTIPROTEASE IMBALANCE IN THE LUNGS OF CHILDREN WITH CYSTIC-FIBROSIS
PROTEASE-ANTIPROTEASE IMBALANCE IN THE LUNGS OF CHILDREN WITH CYSTIC-FIBROSIS
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DOI：
10.1164/ajrccm.150.1.7912987
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发表时间：
1994-07-01
影响因子：
24.7
通讯作者：
CRYSTAL, RG
中科院分区：
文献类型：
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作者：
BIRRER, P;MCELVANEY, NG;CRYSTAL, RG
囊性纤维化(CF)以慢性化脓性支气管炎为特征，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细胞表面释放的中性粒细胞弹性蛋白酶(NE)在本病的发病机制中起重要作用。这项研究试图确定慢性中性粒细胞主导的炎症在CF中的发病年龄及其对CF肺呼吸道上皮表面NE-抗NE筛查的影响。对27例1~18岁稳定期CF患儿的呼吸道上皮液(ELF)中NE和抗NE防御分子进行了检测。尽管α1-抗胰蛋白酶(α1AT)和分泌型白蛋白水解酶抑制物(SLPI)的抗原性浓度正常，但27例CF患儿中有25例以中性粒细胞为主的炎症(>；500个中性粒细胞/亩L ELF)。27名儿童中有20名在ELF中发现了活跃的NE，包括4名1岁儿童中的2名。Western印迹分析显示，大部分α1AT和SLPI分子被络合和/或降解。这些观察表明，慢性失衡的NE-抗-NE保护屏早期在CF患者的呼吸道上皮表面形成，并可能在1岁时很好地建立，从而可能导致肺损伤。
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/mu l 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.