Lesser M, Padilla M L, Cardozo C
Veterans Affairs Medical Center, Bronx, New York.
Am Rev Respir Dis. 1992 Mar;145(3):661-8. doi: 10.1164/ajrccm/145.3.661.
Current theories of pathogenesis suggest that pulmonary emphysema develops in humans because of progressive loss or derangement of lung elastin through a process mediated by elastolytic enzymes released by inflammatory cells. Neutrophils are considered primary etiologic factors because these cells produce and release two potent serine proteinases that cause emphysema when instilled into the lungs of animals. It has been suggested that alveolar macrophages also contribute to the development of emphysema through production of several enzymes with elastolytic activity, including the lysosomal cysteine proteinases cathepsin B and cathepsin L, but this has not been verified experimentally. In the current study, we instilled 115 micrograms of active cathepsin B into the lungs of hamsters three times at 48-h intervals. After 6 wk microscopic evaluation revealed that lung sections of five of seven animals given cathepsin B contained focal areas of enlarged and distorted alveoli, in the absence of fibrosis, which were similar to changes seen in the lungs of animals given papain intratracheally. Morphometrically, mean linear intercept (micron) values were significantly higher (p less than 0.025) in animals given cathepsin B (204.4 +/- 20.8) as compared with control animals (173.2 +/- 7.8), and internal surface area (sqcm) values were significantly lower (935 +/- 120 versus 1,083 +/- 56 in control animals), thereby confirming that airspace enlargement had developed after instillation of the enzyme. Lung volumes (ml) and compliance (ml/cm H2O) were not significantly higher in animals given cathepsin B.(ABSTRACT TRUNCATED AT 250 WORDS)
目前的发病机制理论表明，人类肺气肿的发生是由于肺弹性蛋白通过炎症细胞释放的弹性溶解酶介导的过程进行性丧失或紊乱所致。中性粒细胞被认为是主要病因，因为这些细胞产生并释放两种强效丝氨酸蛋白酶，当注入动物肺部时会导致肺气肿。有人提出肺泡巨噬细胞也通过产生几种具有弹性溶解活性的酶，包括溶酶体半胱氨酸蛋白酶组织蛋白酶B和组织蛋白酶L，促进肺气肿的发展，但这尚未得到实验验证。在本研究中，我们以48小时间隔向仓鼠肺部三次注入115微克活性组织蛋白酶B。6周后，显微镜评估显示，接受组织蛋白酶B的7只动物中有5只的肺切片包含局灶性扩大和扭曲的肺泡区域，无纤维化，这与气管内给予木瓜蛋白酶的动物肺部所见变化相似。形态学上，接受组织蛋白酶B的动物（204.4±20.8）的平均线性截距（微米）值显著高于对照动物（173.2±7.8）（p<0.025），内表面积（平方厘米）值显著低于对照动物（分别为935±120和1083±56），从而证实注入该酶后出现了气腔扩大。接受组织蛋白酶B的动物的肺容积（毫升）和顺应性（毫升/厘米水柱）没有显著升高。（摘要截短至250字）
