Takeyabu K, Betsuyaku T, Nishimura M, Yoshioka A, Tanino M, Miyamoto K, Kawakami Y
First Dept of Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Eur Respir J. 1998 Nov;12(5):1033-9. doi: 10.1183/09031936.98.12051033.
This study examined the role of cysteine proteinases and their inhibitor in the development of emphysema in comparison with neutrophil elastase (NE) complexed with alpha1-protease inhibitor (NE-alpha1-PI), which was previously demonstrated to be increased in bronchoalveolar lavage (BAL) fluid from subjects with subclinical emphysema. Eight nonsmokers and 31 current smokers with (n=17) and without (n=14) emphysema, as evidenced by lung computed tomographic scans, were studied. The concentrations of immunologically detected cathepsin L and cystatin C, but not cathepsin B, were significantly increased in BAL fluid from the smokers with emphysema compared with those without emphysema, although the activity of cathepsin L, measured using a synthetic substrate and cathepsin L, released from cultured alveolar macrophages at 24 h, did not show any significant difference between the two groups. When comparison was made only for the subjects aged <60 yrs, the difference between the two groups disappeared for cathepsin L, but remained for NE-alpha1-PI. There was no significant correlation between the level of cathepsin L and that of NE-alpha1-PI in BAL fluid from the subjects with emphysema. In conclusion, increased levels of cathepsin L and cystatin C were demonstrated in bronchoalveolar lavage fluid from subjects with subclinical emphysema. However, the roles of cathepsin L and neutrophil elastase in the development of emphysema may vary between subjects and between the young and the old.
本研究检测了半胱氨酸蛋白酶及其抑制剂在肺气肿发展过程中的作用,并与先前已证实在亚临床肺气肿患者支气管肺泡灌洗(BAL)液中增加的与α1-蛋白酶抑制剂复合的中性粒细胞弹性蛋白酶(NE-α1-PI)进行比较。研究对象包括8名不吸烟者和31名现吸烟者,其中有肺气肿者(n = 17)和无肺气肿者(n = 14),肺气肿由肺部计算机断层扫描证实。与无肺气肿的吸烟者相比,有肺气肿的吸烟者BAL液中免疫检测到的组织蛋白酶L和胱抑素C的浓度显著升高,但组织蛋白酶B的浓度未升高。尽管使用合成底物测量的组织蛋白酶L的活性以及在24小时从培养的肺泡巨噬细胞释放的组织蛋白酶L在两组之间没有显示出任何显著差异。仅对年龄<60岁的受试者进行比较时,两组之间组织蛋白酶L的差异消失,但NE-α1-PI的差异仍然存在。在有肺气肿的受试者的BAL液中,组织蛋白酶L水平与NE-α1-PI水平之间没有显著相关性。总之,在亚临床肺气肿患者的支气管肺泡灌洗液中证实了组织蛋白酶L和胱抑素C水平升高。然而,组织蛋白酶L和中性粒细胞弹性蛋白酶在肺气肿发展中的作用可能因受试者以及年轻人和老年人而异。