MMP-2-and MMP-9-linked gelatinolytic activity in the sputum from patients with asthma and chronic obstructive pulmonary disease
MMP-2-and MMP-9-linked gelatinolytic activity in the sputum from patients with asthma and chronic obstructive pulmonary disease
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DOI：
10.1159/000024452
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发表时间：
2000-11-01
影响因子：
2.8
通讯作者：
Louis, R
中科院分区：
文献类型：
--
作者：
Cataldo, D;Munaut, C;Louis, R
背景：哮喘和慢性阻塞性肺疾病（COPD）的病程与支气管形态学改变有关。金属蛋白酶被认为在这些结构变化中发挥作用。方法：对20例哮喘患者、20例COPD患者和19例健康对照者的诱导痰进行明胶酶活性检测。通过定量酶谱法进行明胶分解活性的评估，并通过Western印迹分析鉴定明胶分解物种。采用反向酶谱法和酶联免疫吸附法（ELISA）检测组织金属蛋白酶抑制剂-1（TIMP-1）。结果如下：从酶谱分析，我们发现与对照组相比，哮喘患者（p < 0.0001）和COPD患者（p <0.0001）的痰中与基质金属蛋白酶原-9（pro-MMP-9）相关的明胶分解活性显著更高。此外，在60%的哮喘患者和85%的COPD患者的痰中发现了活化形式的MMP-9（85 kD），而在对照组中则不存在（p < 0.0001）。重要的是，尽管pro-MMP-2（72 kD）的检测频率低于pro-MMP-9，但在哮喘患者中（50%）比对照受试者（5%）更频繁地发现pro-MMP-2（p < 0.005）。我们还描述了两个不寻常的明胶溶解物种的45和120 kD，并表明，他们来自MMP-9根据他们的能力，结合明胶和抗MMP-9抗体。哮喘组和COPD组TIMP-1水平均高于对照组（p <0.05）。结论：哮喘和COPD患者显示出与MMP-2和MMP-9相关的明胶分解活性增加，并且其痰中TIMP-1水平较高。版权所有（C）2000 S. Karger AG，巴塞尔。
Background: The course of asthma and chronic obstructive pulmonary disease (COPD) is associated with bronchial morphological changes. Metalloproteinases are thought to play a role in these structural changes. Methods: We studied the gelatinolytic activity present in the induced sputum from 20 patients with asthma, 20 with COPD and 19 healthy controls. The assessment of gelatinolytic activity was performed by quantitative zymography, and gelatinolytic species were identified by Western blot analysis. Tissue inhibitor of metalloproteinase-l (TIMP-1) was detected by reverse zymography and ELISA. Results: From zymography, we found significantly higher gelatinolytic activity linked to pro-matrix metalloproteinase-9 (pro-MMP-9) in the sputum from asthmatics (p < 0.0001) and COPD patients (p < 0.0001) compared to the control group. Furthermore, the activated form of MMP-9 (85 kD) was found in the sputum from 60% of asthmatics and 85% of COPD patients, but was absent in that of control subjects (p < 0.0001). Importantly, although less frequently detectable than pro-MMP-9, pro-MMP-2 (72 kD) was found more frequently in asthmatics (50%) than in control subjects (5%) (p < 0.005). We also described two unusual gelatinolytic species of 45 and 120 kD and showed that they derived from MMP-9 according to their ability to bind gelatin and anti-MMP-9 antibody. Levels of TIMP-1 were higher in asthmatics (p < 0.05) and COPD patients (p < 0.05) than in controls. Conclusion: Asthmatics and COPD patients display an increased gelatinolytic activity linked to MMP-2 and MMP-9 and higher levels of TIMP-1 in their sputum. Copyright (C) 2000 S. Karger AG, Basel.