Extracellular matrix metalloproteinase inducer in interstitial pneumonias

Extracellular matrix metalloproteinase inducer in interstitial pneumonias
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DOI:
10.1016/j.humpath.2006.03.006
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发表时间:
2006-08-01
期刊:
影响因子:
3.3
通讯作者:
Nishimura, Masaharu
Nishimura, Masaharu
中科院分区:
医学3区
文献类型:
--
作者:
Odajima, Nao;Betsuyaku, Tomoko;Nishimura, Masaharu

文献摘要

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细胞外基质金属蛋白酶诱导剂(EMMPRIN)是一种诱导基质金属蛋白酶(MMPs)的糖基化跨膜蛋白,在正常成人肺中表达量极低。我们之前报道了它在博莱霉素诱导的小鼠肺损伤中上调。在本研究中,我们检测了EMMPRIN在间质性肺炎(IPs)中的表达及其与MMP-2、MMP-7和MMP-9的关系。我们对22名不同IPs患者的肺组织进行了EMMPRIN和MMPs的免疫组化。我们对其中9名受试者和13名使用IN的受试者进行了支气管肺泡灌洗(BAL),以测量BAL液中可溶性EMMPRIN的含量。为比较,对14例无IPs的受试者进行免疫组化或BAL。在各种上皮细胞类型中,每种蛋白的染色强度从0到3分。采用酶联免疫吸附法测定BAL液中可溶性EMMPRIN的含量。细胞外基质金属蛋白酶诱导剂在异常上皮细胞中表现突出。与肺泡细支气管增生的上皮细胞相比,它在增生性II型细胞中更为突出。在IPs患者的BAL液中也有升高。基质金属蛋白酶在表达EMMPRIN的细胞中表达,尽管MMPs的分布在不同的异常上皮细胞类型中有所不同,增生性II型细胞中有MMP-2和MMP-7,鳞状化生细胞和细支气管化细胞中有MMP-7和MMP-9。这些结果提示EMMPRIN在IPs细胞的再上皮化中起作用。(c) 2006爱思唯尔公司版权所有。
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 IN 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. (c) 2006 Elsevier Inc. All rights reserved.