The involvement of matrix metalloproteinase-9 in airway inflammation of patients with acute asthma

The involvement of matrix metalloproteinase-9 in airway inflammation of patients with acute asthma
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DOI:
10.1046/j.1365-2222.2001.01211.x
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发表时间:
2001-10-01
影响因子:
6.1
通讯作者:
Song, CH
Song, CH
中科院分区:
医学2区
文献类型:
--
作者:
Lee, YC;Lee, HB;Song, CH

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背景支气管哮喘是一种以气道重塑为特征的气道炎症性疾病,其部分原因是气道壁细胞外基质(extracellular matrix,ECM)过度沉积,导致上皮下胶原沉积。基质金属蛋白酶-9(MMP-9)是哮喘中诱导支气管重塑的主要蛋白水解酶。MMP-9在炎症细胞通过基底膜组分的迁移中也很重要。目的我们评估急性哮喘中气道炎症细胞是否与MMP-9水平相关,并检测自发性哮喘急性发作患者痰液MMP-9活性水平的时间进程。方法我们进行酶谱分析,并通过酶免疫法检测MMP-9水平。MMP-9水平也在哮喘自发发作期间进行了评价。结果哮喘患者血浆MMP-9浓度和MMP-9活性均显著高于正常对照组(P < 0.01)。哮喘急性期患者血浆MMP-9活性显著高于哮喘稳定期患者(P < 0.01)。MMP-9活性在治疗7天和28天后显著降低。结论哮喘急性发作后气道炎症与MMP-9的过度表达有关,MMP-9的过度表达导致气道重塑。
Background Bronchial asthma is an inflammatory disease of the airway characterized by airway remodelling, and is due at least in part to an excess of extracellular matrix (ECM) deposition in the airway wall, which leads to subepithelial collagen deposition. Matrix metalloproteinase-9 (MMP-9) is the major proteolytic enzyme that induces bronchial remodelling in asthma. MMP-9 is also important in the migration of inflammatory cells through basement membrane components.Objectives We evaluated whether airway inflammatory cells correlated with levels of MMP-9 in acute asthma and we examined the time course of sputum levels of MMP-9 activity in patients with spontaneous asthma exacerbation.Methods We performed zymographic analysis and checked levels of MMP-9 by means of enzyme immunoassay. MMP-9 levels were also evaluated during a spontaneous attack of asthma. Results Pro-MMP-9 activities and concentrations of MMP-9 in asthmatic patients significantly exceeded those of control subjects (P < 0.01). The activities of pro-MMP-9 were significantly higher in acute asthmatic patients than in stable asthmatic patients (P < 0.01). The elevated MMP-9 activities significantly decreased after 7 and 28 days of therapy. In acute asthmatic patients, the levels of sputum MMP-9 significantly correlated with the total macrophage + neutrophil + eosinophil cell numbers.Conclusion These data suggest that airway inflammation after asthma exacerbation correlates with the overproduction of MMP-9, which then leads to airway remodelling.