Venaille T J, Ryan G, Robinson B W
University Department of Medicine, QEII Medical Centre, Perth, Western Australia.
Respir Med. 1998 Feb;92(2):233-40. doi: 10.1016/s0954-6111(98)90101-9.
Airway histopathological changes in cystic fibrosis (CF) include damage to the epithelial tissue and accumulation of polymorphonuclear leukocytes (PMN). Airways of CF patients are usually colonized with bacteria such as mucoid Pseudomonas aeruginosa (PA). Bacteria and PMN can both release proteolytic enzymes capable of causing tissue damage. This study aims to clarify and compare the roles of these agents in epithelium damage. Epithelial cell (EC) damage and detachment induced by sputum samples from CF or non-CF patients, with and without lung infection, were assessed on amnionic EC in an in vitro model of airway epithelium. Protease activity was determined using inhibitor profiles, and compared to the proteolytic activity of isolated neutrophils and bacteria. Sputa from CF patients and infected non-CF patients induced high levels of detachment. PA also induced high levels of EC detachment but Staphylococcus aureus and Haemophilus influenzae, two other bacteria commonly isolated from CF sputa, induced no detachment. Antiprotease inhibition profiles were similar for PMN and sputa-induced EC detachment, but different for PA-induced detachment. These results suggest that PMN proteolytic enzymes, probably elastase and cathepsin G, are more likely to be the inducers of tissue damage in the airways of CF patients than PA proteolytic enzymes.
囊性纤维化（CF）患者气道的组织病理学变化包括上皮组织损伤和多形核白细胞（PMN）积聚。CF患者的气道通常会被黏液样铜绿假单胞菌（PA）等细菌定植。细菌和PMN均可释放能够导致组织损伤的蛋白水解酶。本研究旨在阐明并比较这些因子在上皮损伤中的作用。在气道上皮的体外模型中，对来自CF或非CF患者、有无肺部感染的痰液样本诱导羊膜上皮细胞（EC）损伤和脱离的情况进行了评估。使用抑制剂谱测定蛋白酶活性，并与分离的中性粒细胞和细菌的蛋白水解活性进行比较。CF患者和感染的非CF患者的痰液诱导了高水平的脱离。PA也诱导了高水平的EC脱离，但从CF痰液中常见分离出的另外两种细菌——金黄色葡萄球菌和流感嗜血杆菌，并未诱导脱离。PMN和痰液诱导的EC脱离的抗蛋白酶抑制谱相似，但PA诱导的脱离则不同。这些结果表明，与PA蛋白水解酶相比，PMN蛋白水解酶（可能是弹性蛋白酶和组织蛋白酶G）更有可能是CF患者气道组织损伤的诱导因素。
