Odajima Nao, Betsuyaku Tomoko, Nasuhara Yasuyuki, Itoh Tomoo, Fukuda Yuh, Senior Robert M, Nishimura Masaharu
First Department of Medicine, Hokkaido University Hospital, Sapporo 060-8638, Japan.
Hum Pathol. 2006 Aug;37(8):1058-65. doi: 10.1016/j.humpath.2006.03.006. Epub 2006 Jun 2.
Extracellular matrix metalloproteinase inducer (EMMPRIN), a glycosylated transmembrane protein that induces matrix metalloproteinases (MMPs), is minimally expressed in the normal adult lung. We previously reported that it is up-regulated in murine bleomycin-induced lung injury. In this study, we determined the expression of EMMPRIN and its association with MMP-2, MMP-7, and MMP-9 in interstitial pneumonias (IPs). We performed immunohistochemistry for EMMPRIN and MMPs on lung tissue from 22 subjects with various IPs. We did bronchoalveolar lavage (BAL) on 9 of these subjects and 13 others with IPs to measure the soluble EMMPRIN in BAL fluid. For comparison, immunohistochemistry or BAL was done on 14 subjects without IPs. The staining intensity for each protein was scored from 0 to 3 in various epithelial cell types. Soluble EMMPRIN in BAL fluid was measured by an enzyme-linked immunosorbent assay. Extracellular matrix metalloproteinase inducer was prominent in abnormal epithelial cells. It was more prominent in hyperplastic type II cells, compared with epithelium in alveolar bronchiolization. It was also elevated in BAL fluid from the subjects with IPs. Matrix metalloproteinases were expressed in cells expressing EMMPRIN, although the profile of MMPs varied among the different abnormal epithelial cell types with MMP-2 and MMP-7 in hyperplastic type II cells and MMP-7 and MMP-9 in cells showing squamous metaplasia and cells comprising bronchiolization. These results suggest a role of EMMPRIN in reepithelialization in IPs.
细胞外基质金属蛋白酶诱导剂(EMMPRIN)是一种可诱导基质金属蛋白酶(MMPs)的糖基化跨膜蛋白,在正常成年肺组织中表达极少。我们之前报道过它在小鼠博来霉素诱导的肺损伤中上调。在本研究中,我们测定了间质性肺炎(IPs)中EMMPRIN的表达及其与MMP - 2、MMP - 7和MMP - 9的关联。我们对22例患有各种IPs的受试者的肺组织进行了EMMPRIN和MMPs的免疫组织化学检测。我们对其中9例受试者以及另外13例患有IPs的受试者进行了支气管肺泡灌洗(BAL),以测量灌洗液中的可溶性EMMPRIN。作为对照,对14例无IPs的受试者进行了免疫组织化学检测或BAL。对各种上皮细胞类型中每种蛋白的染色强度从0到3进行评分。通过酶联免疫吸附测定法测量BAL液中的可溶性EMMPRIN。细胞外基质金属蛋白酶诱导剂在异常上皮细胞中显著表达。与肺泡细支气管化中的上皮相比,在增生性II型细胞中更显著。在患有IPs的受试者的BAL液中也升高。基质金属蛋白酶在表达EMMPRIN的细胞中表达,尽管不同异常上皮细胞类型中MMPs的表达谱有所不同,增生性II型细胞中为MMP - 2和MMP - 7,鳞状化生细胞和构成细支气管化的细胞中为MMP - 7和MMP - 9。这些结果表明EMMPRIN在IPs的再上皮化过程中发挥作用。