哮喘急性加重期循环中92 kDa基质金属蛋白酶（MMP-9）活性增加。
Increased circulating 92 kDa matrix metalloproteinase (MMP-9) activity in exacerbations of asthma.
作者信息
Oshita Y, Koga T, Kamimura T, Matsuo K, Rikimaru T, Aizawa H
机构信息
First Department of Internal Medicine, Kurume University School of Medicine, 67 Asahimachi, Kurume 830-0011, Japan.
出版信息
Thorax. 2003 Sep;58(9):757-60. doi: 10.1136/thorax.58.9.757.
BACKGROUND
The 72 kDa matrix metalloproteinase 2 (MMP-2) and the 92 kDa matrix metalloproteinase 9 (MMP-9) are type IV collagenases implicated in various aspects of inflammation including accumulation of inflammatory cells, tissue injury, and development of remodelling. The role of these enzymes in the pathogenesis of asthma exacerbations is unknown.
METHODS
Circulating levels of MMP-2 and MMP-9 proteins and the expression of their inhibitor, tissue inhibitor of metalloproteinase 1 (TIMP-1), were measured in 21 patients experiencing an asthma exacerbation and 21 age matched patients with stable asthma. Circulating gelatinolytic activity was compared during the asthma exacerbation and during subsequent convalescence by gelatin zymography in the same individuals. In addition, MMP-9 specific activity was quantified with a colorimetric assay which uses an artificial proenzyme containing a specific domain recognised by MMP-9 in the same paired samples.
RESULTS
A significant increase in the circulating level of MMP-9 was seen in patients with an asthma exacerbation compared with patients with stable asthma (202.9 (22.0) v 107.7 (9.9) ng/ml, p=0.0003). There were no significant differences in the circulating levels of MMP-2 or TIMP-1. Gelatin zymography identified two major circulating gelatinolytic activities corresponding to MMP-2 and MMP-9, and showed that asthma exacerbations are characterised by markedly increased MMP-9 activity with no significant change in MMP-2 activity compared with the activities during convalescence in the same individuals. Direct measurement showed that MMP-9 specific activity is significantly increased during asthma exacerbations compared with subsequent convalescence (269.6 (31.7) v 170.4 (12.6) ng/ml, p=0.0099).
CONCLUSIONS
Asthma exacerbations are characterised by increased circulating MMP-9 activity. This increased activity may be related to exaggerated airway inflammation and airway remodelling.
背景
72kDa基质金属蛋白酶2（MMP-2）和92kDa基质金属蛋白酶9（MMP-9）是IV型胶原酶，与炎症的各个方面有关，包括炎症细胞的积聚、组织损伤和重塑的发展。这些酶在哮喘急性发作发病机制中的作用尚不清楚。
方法
测量了21例哮喘急性发作患者和21例年龄匹配的稳定期哮喘患者循环中MMP-2和MMP-9蛋白水平及其抑制剂金属蛋白酶组织抑制剂1（TIMP-1）的表达。通过明胶酶谱法比较了同一患者哮喘急性发作期和随后恢复期的循环明胶酶活性。此外，在同一配对样本中，采用比色法对MMP-9的特异性活性进行了定量，该方法使用一种含有MMP-9识别的特定结构域的人工酶原。
结果
与稳定期哮喘患者相比，哮喘急性发作患者循环中MMP-9水平显著升高（202.9（22.0）对107.7（9.9）ng/ml，p=0.0003）。MMP-2或TIMP-1的循环水平无显著差异。明胶酶谱法鉴定出两种主要的循环明胶酶活性，分别对应于MMP-2和MMP-9，并显示哮喘急性发作的特征是MMP-9活性显著增加，与同一患者恢复期的活性相比，MMP-2活性无显著变化。直接测量显示，与随后的恢复期相比，哮喘急性发作期MMP-9的特异性活性显著增加（269.6（31.7）对170.4（12.6）ng/ml，p=0.0099）。
结论
哮喘急性发作的特征是循环中MMP-9活性增加。这种活性增加可能与气道炎症和气道重塑加剧有关。
Zotero 插件