Elevated MMP-12 protein levels in induced sputum from patients with COPD
Elevated MMP-12 protein levels in induced sputum from patients with COPD
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DOI：
10.1136/thx.2005.042432
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发表时间：
2006-03-01
期刊：
影响因子：
10
通讯作者：
Brusselle, GG
中科院分区：
文献类型：
--
作者：
Demedts, IK;Morel-Montero, A;Brusselle, GG
背景：多种基质金属蛋白酶（MMPs）参与慢性阻塞性肺疾病（COPD）的发病机制。在小鼠中，MMP-12在香烟引起的肺气肿的发展中起着至关重要的作用。一项研究调查了MMP-12在人类吸烟者COPD发展中的作用。方法：收集稳定期COPD患者（28例）、健康吸烟者（14例）、从不吸烟者（20例）和已戒烟者（14例）的诱导痰样本。采用ELISA法测定诱导痰中MMP-12蛋白水平，并比较4个研究组间的差异。通过酪蛋白酶谱法和荧光淬灭底物的切割来评估诱导痰中MMP-12酶活性。结果：COPD患者的中位（IQR） MMP-12水平显著高于健康吸烟者、从不吸烟者和曾经吸烟者(17.5 (7.1 - 42.1)v 6.7 (3.9 - 10.4) v 4.2 （2.4 - 11.3) v 6.1 (4.5 - 7.6) ng/ml, p = 0.0002）。COPD患者的MMP-12酶活性显著高于对照组(4.11 （1.4 - 8.0)v 0.14 (0.1 - 0.2) mu g/ml, p = 0.0002）。结论：与对照组相比，MMP-12在稳定期COPD患者诱导痰中明显升高，提示MMP-12在吸烟者COPD发展中起作用。
Background: Several matrix metalloproteinases ( MMPs) are involved in the pathogenesis of chronic obstructive pulmonary disease ( COPD). In mice, MMP-12 plays a crucial role in the development of cigarette smoke induced emphysema. A study was undertaken to investigate the role of MMP-12 in the development of COPD in human smokers.Methods: Induced sputum samples were collected from patients with stable COPD (n = 28), healthy smokers ( n = 14), never smokers ( n = 20), and former smokers ( n = 14). MMP-12 protein levels in induced sputum were determined by ELISA and compared between the four study groups. MMP-12 enzymatic activity in induced sputum was evaluated by casein zymography and by cleaving of a fluorescence quenched substrate.Results: Median (IQR) MMP-12 levels were significantly higher in COPD patients than in healthy smokers, never smokers, and former smokers (17.5 (7.1 - 42.1) v 6.7 (3.9 - 10.4) v 4.2 (2.4 - 11.3) v 6.1 (4.5 - 7.6) ng/ml, p = 0.0002). MMP-12 enzymatic activity was significantly higher in patients with COPD than in controls (4.11 (1.4 - 8.0) v 0.14 (0.1 - 0.2) mu g/ml, p = 0.0002).Conclusion: MMP-12 is markedly increased in induced sputum from patients with stable COPD compared with controls, suggesting a role for MMP-12 in the development of COPD in smokers.