Identification of Uteroglobin-Related Protein 1 and Macrophage Scavenger Receptor with Collagenous Structure as a Lung-Specific Ligand-Receptor Pair1

Identification of Uteroglobin-Related Protein 1 and Macrophage Scavenger Receptor with Collagenous Structure as a Lung-Specific Ligand-Receptor Pair1
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鉴定子宫珠蛋白相关蛋白 1 和具有胶原结构的巨噬细胞清道夫受体作为肺特异性配体-受体对1

DOI:
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发表时间:
2003
影响因子:
4.4
通讯作者:
H. Shu
H. Shu
中科院分区:
医学2区
文献类型:
--
作者:
Liang;Larry D. Nielson;Xinqi Liu;R. Mason;H. Shu

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正常高表达(High in Normal,HIN)-1是一种分泌型蛋白,在正常乳腺上皮中高表达,在乳腺癌中表达下调。通过搜索GenBank表达序列标签数据库,我们鉴定到与HIN-1同源的蛋白质HIN-2。Hin-2与最近发现的一种名为子宫球蛋白相关蛋白1(UGRP1)的蛋白质相同。Northern印迹分析表明,UGRP1在肺组织中特异表达,而在其他组织中不表达。原位杂交实验表明,UGRP1表达于肺内Clara样细胞,并在囊性纤维化中表达上调。在哺乳动物表达系统中,分泌型重组UGRP1与载脂蛋白A-I共表达。利用逆转录病毒载体介导的表达克隆方法,我们鉴定了具有胶原性结构的巨噬细胞清道夫受体(MARCO)为UGRP1的受体。Northern印迹和原位杂交实验表明,肺泡巨噬细胞表达Marco。UGRP1还与细菌和酵母结合。LPs是以前发现的Marco配体,与UGRP1竞争与Marco和细菌的结合。我们的发现表明,UGRP1-MARCO是一对配体-受体对,可能参与肺部的炎症和病原体清除。
High in normal (HIN)-1 is a secreted protein highly expressed in normal breast epithelium and down-regulated in breast carcinomas. By searching GenBank expressed sequence tag databases, we identified HIN-2, a protein homologous to HIN-1. HIN-2 is identical with a recently identified protein called uteroglobin-related protein 1 (UGRP1). Northern blot analysis demonstrated that UGRP1 is specifically expressed by lung, but not by the other tissues examined. By in situ hybridization experiments, UGRP1 was shown to be expressed by lung Clara-like cells in the bronchial epithelium and to be up-regulated in cystic fibrosis. In a mammalian expression system, secreted recombinant UGRP1 was copurified with apolipoprotein A-I. Using a retroviral vector-mediated expression cloning approach, we identified macrophage scavenger receptor with collagenous structure (MARCO) as a receptor for UGRP1. Northern blot and in situ hybridization experiments indicated that MARCO is expressed by alveolar macrophages in the lung. UGRP1 also bound to bacteria and yeast. LPS, a previously identified MARCO ligand, competed with UGRP1 for binding to MARCO and bacteria. Our findings suggest that UGRP1-MARCO is a ligand-receptor pair that is probably involved in inflammation and pathogen clearance in the lung.
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