Cataldo Didier D, Bettiol Jane, Noël Agnes, Bartsch Pierre, Foidart Jean-Michel, Louis Renaud
Departments of Pneumology, University of Liège, Liège, Belgium.
Chest. 2002 Nov;122(5):1553-9. doi: 10.1378/chest.122.5.1553.
The aim of the study was to determine whether allergen inhalation modulates the levels of matrix metalloproteinase (MMP)-9 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 in the induced sputum recovered from patients during a late-phase reaction.
Eight allergic asthma patients and five healthy control subjects inhaled a dose of Dermatophagoides pteronyssinus extract corresponding to the provocative concentration of the allergen causing a 20% fall in FEV(1) and saline solution. Lung function was carefully monitored for 6 h, and an induced sputum test was performed at 6 h after sham challenge or allergen challenge. The total and differential cell counts were analyzed, and the levels of MMP-9 (by enzyme-linked immunosorbent assay [ELISA] and zymography), TIMP-1 (by ELISA), and albumin (by rocket immunoelectrophoresis) were measured.
The sputum eosinophil counts (p < 0.01) and MMP-9 levels (p < 0.05) increased significantly in atopic asthma patients after undergoing the allergen challenge but did not in the control subjects. By contrast, TIMP-1 and albumin levels were not significantly increased in any group. MMP-9 levels, measured after the allergen challenge in asthmatic patients, were significantly correlated with FEV(1) variations after allergen inhalation (r = 0.51; p < 0.05) and with the sputum neutrophil percentage (r = 0.71; p < 0.01).
The levels of MMP-9, but not TIMP-1, increase after inhaled allergen challenge in the sputum of allergic asthmatic patients. This protease increase may lead to a transient imbalance between MMP-9 and TIMP-1 favoring proteolytic extracellular matrix degradation.
本研究旨在确定变应原吸入是否会调节迟发相反应期间从患者诱导痰中回收的基质金属蛋白酶(MMP)-9和基质金属蛋白酶组织抑制剂(TIMP)-1的水平。
8名过敏性哮喘患者和5名健康对照受试者吸入一剂与引起FEV(1)下降20%的变应原激发浓度相当的屋尘螨提取物和盐溶液。仔细监测肺功能6小时,并在假激发或变应原激发后6小时进行诱导痰试验。分析总细胞计数和分类细胞计数,并测量MMP-9(通过酶联免疫吸附测定[ELISA]和酶谱法)、TIMP-1(通过ELISA)和白蛋白(通过火箭免疫电泳)的水平。
变应原激发后,特应性哮喘患者的痰嗜酸性粒细胞计数(p<0.0t)和MMP-9水平(p<0.05)显著升高,而对照组未升高。相比之下,任何组的TIMP-1和白蛋白水平均未显著升高。哮喘患者变应原激发后测得的MMP-9水平与变应原吸入后的FEV(1)变化显著相关(r=0.51;p<0.05),与痰中性粒细胞百分比显著相关(r=0.71;p<0.01)。
过敏性哮喘患者吸入变应原激发后,痰中MMP-9水平升高,而TIMP-1水平未升高。这种蛋白酶增加可能导致MMP-9和TIMP-1之间的短暂失衡,有利于细胞外基质的蛋白水解降解。