Vuorinen Kirsi, Myllärniemi Marjukka, Lammi Lauri, Piirilä Päivi, Rytilä Paula, Salmenkivi Kaisa, Kinnula Vuokko L
Department of Medicine and Division of Pulmonary Medicine, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
APMIS. 2007 Aug;115(8):969-75. doi: 10.1111/j.1600-0463.2007.apm_697.x.
Microarray studies have shown that matrilysin or matrix metalloproteinase (MMP)-7 is highly upregulated in the lungs of patients with idiopathic pulmonary fibrosis (IPF), but MMP-7 protein expression has not been systematically compared between IPF and other interstitial lung diseases. MMP-7 levels in bronchoalveolar lavage fluid (BALF) were compared to corresponding samples from nonspecific interstitial pneumonia (NSIP), sarcoidosis, and healthy controls. MMP-7 levels in the BALF were determined by ELISA and localization of MMP-7 in the lung tissue by immunohistochemistry. MMP-7 was similarly elevated in the BALF of all these disorders compared to healthy controls (p=0.007). Even control subjects with prolonged cough displayed a tendency towards elevated MMP-7 expression. There was a negative correlation between BALF MMP-7 levels and forced expiratory vital capacity (r=-0.348, p=0.02, n=42). In IPF lung, MMP-7 immunoreactivity appeared predominantly in the fibrotic parenchyma and arterial wall. In sarcoidosis and NSIP, prominent MMP-7 immunoreactivity was found in areas of inflammation. These results demonstrate that elevated BALF MMP-7 is not restricted to IPF alone but is also observed in other interstitial lung diseases and cannot be used as a differential diagnostic marker for IPF.
微阵列研究表明,基质溶素或基质金属蛋白酶(MMP)-7在特发性肺纤维化(IPF)患者的肺组织中高度上调,但尚未对IPF与其他间质性肺疾病之间的MMP-7蛋白表达进行系统比较。将支气管肺泡灌洗液(BALF)中的MMP-7水平与非特异性间质性肺炎(NSIP)、结节病患者以及健康对照者的相应样本进行比较。通过酶联免疫吸附测定(ELISA)法测定BALF中的MMP-7水平,并通过免疫组织化学法确定肺组织中MMP-7的定位。与健康对照者相比,所有这些疾病的BALF中MMP-7水平均同样升高(p = 0.007)。甚至咳嗽时间延长的对照受试者也呈现出MMP-7表达升高的趋势。BALF中MMP-7水平与用力呼气肺活量呈负相关(r = -0.348,p = 0.02,n = 42)。在IPF肺组织中,MMP-7免疫反应主要出现在纤维化实质和动脉壁中。在结节病和NSIP中,在炎症区域发现了明显的MMP-7免疫反应。这些结果表明,BALF中MMP-7升高并非IPF所特有,在其他间质性肺疾病中也可观察到,因此不能用作IPF的鉴别诊断标志物。