Characteristic elevation of matrix metalloproteinase activity in idiopathic interstitial pneumonias
Characteristic elevation of matrix metalloproteinase activity in idiopathic interstitial pneumonias
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DOI：
10.1164/ajrccm.162.5.9906096
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发表时间：
2000-11-01
影响因子：
24.7
通讯作者：
Ando, M
中科院分区：
文献类型：
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作者：
Suga, M;Iyonaga, K;Ando, M
上皮下基底膜的破坏是特发性肺纤维化(IPF)发病机制中的关键事件。为探讨基质金属蛋白酶(MMPs)在特发性间质性肺炎(IIP)实质重塑中的作用，采用酶谱法检测BALF中MMP2、MMP9活性，免疫组织化学法检测肺组织中MMP2、TIMP-2的表达。收集26例普通型间质性肺炎(IPF-UIP)、11例非特异性间质性肺炎(NSIP)和6例闭塞性细支气管炎机化性肺炎(BOOP)患者的BALF和肺组织标本。IPF-UIP组在BALF-UIP组织中主要表达MMP9，而NSIP组和BOOP组BALF及组织中MMP2主要表达。在快速进展的IPF-UIP病例的BALF样本中，特征性地检测到中性粒细胞来源的基质金属蛋白酶-9活性以及基质金属蛋白酶-9的活性形式。此外，MMP9活性与BALF中性粒细胞的增加显著相关，而与NSIP和BOOP相关的MMP2活性与淋巴细胞的增加显著相关。提示IPF-UIP中的MMP9和NSIP中的MMP2和BOOP中的MMP2可能通过IV型胶原酶活性参与肺结构重建。基质降解蛋白的特征贡献可能与这些疾病的不同预后特征有关。
Destruction of subepithelial basement membrane is a key event in the pathogenesis of idiopathic pulmonary fibrosis (IPF). To evaluate the role of matrix metalloproteinases (MMPs) in parenchymal remodeling in idiopathic interstitial pneumonia (IIP), we studied MMP-2 and -9 activity, in bronchoalveolar lavage fluid (BALF) by zymography and the expression of MMP-2 and -9 and TIMP-2 in lung tissue by immunohistochemistry. BALF and lung tissues were collected from 26 patients with usual interstitial pneumonia (IPF-UIP), 11 with nonspecific interstitial pneumonia (NSIP), and 6 with bronchiolitis obliterans organizing pneumonia (BOOP). IPF-UIP cases showed predominant expression of MMP-9, whereas NSIP and BOOP cases showed predominant MMP-2 expression in BALF and in tissues. In BALF samples from rapidly progressive IPF-UIP cases, neutrophil-derived MMP-9 activity, as well as MMP-9 active form were characteristically detected. Furthermore, the MMP-9 activity correlated significantly with an increase of neutrophils in BALF, whereas the MMP-2 activity associated with NSIP and BOOP correlated with an increase of lymphocytes. These results indicate that MMP-9 in IPF-UIP and MMP-2 in NSIP and BOOP may contribute to pulmonary structural remodeling through type IV collagenolytic activity. The characteristic contributions of matrix-degrading proteins may relate to the distinct prognostic features of these diseases.