Alveolar macrophage-mediated elastolysis: roles of matrix metalloproteinases, cysteine, and serine proteases
Alveolar macrophage-mediated elastolysis: roles of matrix metalloproteinases, cysteine, and serine proteases
复制标题
DOI：
10.1152/ajplung.00020.2002
复制
发表时间：
2002-10-01
影响因子：
4.9
通讯作者：
Barnes, PJ
中科院分区：
文献类型：
--
作者：
Russell, REK;Thorley, A;Barnes, PJ
慢性阻塞性肺疾病（COPD）是一种常见的肺部疾病，吸烟是主要病因，但只有15%的吸烟者罹患慢性阻塞性肺病。 COPD 中观察到的肺弹性蛋白破坏是由许多酶介导的，包括半胱氨酸、丝氨酸和基质金属蛋白酶 (MMP)。这些酶对从非吸烟者、健康吸烟者和慢性阻塞性肺病患者收集的肺泡巨噬细胞释放的肺弹力分解负荷的贡献，通过放射性标记的弹性蛋白作为底物在特定酶抑制剂存在下进行检查。通过酶谱法和蛋白质印迹进一步检查MMP的活性。慢性阻塞性肺病巨噬细胞比其他群体降解更多的弹性蛋白。最初的 24 小时弹性组织溶解最大。在 72 小时的培养期间，丝氨酸弹性蛋白酶对弹性组织溶解的贡献下降，MMP 增加，而半胱氨酸弹性蛋白酶保持不变。慢性阻塞性肺病患者体内弹性酶释放的增加可以解释为什么一些吸烟者会患上慢性阻塞性肺病。这种差异可能是由于未知的易感因素造成的。丝氨酸蛋白酶发挥着重要作用；然而，其他酶，特别是 MMP，值得进一步研究。
Chronic obstructive pulmonary disease (COPD) is a common lung disease with cigarette smoking as the major etiological factor, but only 15% of smokers develop COPD. Destruction of lung elastin observed in COPD is mediated by many enzymes, including cysteine, serine, and matrix metalloproteinases (MMP). The contribution of these enzymes to the lung elastolytic load, released from alveolar macrophages collected from nonsmokers, healthy smokers, and COPD patients, was examined by radiolabeled elastin as substrate in the presence of specific enzyme inhibitors. The activity of MMP was further examined by zymography and Western blotting. COPD macrophages degraded more elastin than either of the other groups. Elastolysis was greatest in the initial 24 h. Through the 72-h culture period, the contribution to elastolysis of serine elastases decreased, MMP increased, and cysteine elastases remained constant. The increased release of elastolytic enzymes in COPD subjects may explain why some smokers develop COPD. This difference may be due to unknown susceptibility factors. Serine proteases play a significant role; however, other enzymes, particularly the MMP, deserve further investigation.