Bin Liang-Hua, Nielson Larry D, Liu Xinqi, Mason Robert J, Shu Hong-Bing
Department of Immunology, National Jewish Medical and Research Center, University of Colorado Health Sciences Center, Denver, CO 80206, USA.
J Immunol. 2003 Jul 15;171(2):924-30. doi: 10.4049/jimmunol.171.2.924.
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.
正常高表达（HIN）-1是一种分泌蛋白，在正常乳腺上皮中高度表达，而在乳腺癌中表达下调。通过搜索GenBank表达序列标签数据库，我们鉴定出了HIN-2，一种与HIN-1同源的蛋白质。HIN-2与最近鉴定出的一种名为子宫珠蛋白相关蛋白1（UGRP1）的蛋白质相同。Northern印迹分析表明，UGRP1在肺中特异性表达，而在所检测的其他组织中不表达。通过原位杂交实验，发现UGRP1在支气管上皮的肺克拉拉样细胞中表达，并在囊性纤维化中上调。在哺乳动物表达系统中，分泌型重组UGRP1与载脂蛋白A-I共纯化。使用逆转录病毒载体介导的表达克隆方法，我们鉴定出具有胶原结构的巨噬细胞清道夫受体（MARCO）作为UGRP1的受体。Northern印迹和原位杂交实验表明，MARCO在肺中的肺泡巨噬细胞中表达。UGRP1也与细菌和酵母结合。脂多糖（LPS）是先前鉴定出的MARCO配体，它与UGRP1竞争与MARCO和细菌的结合。我们的研究结果表明，UGRP1-MARCO是一个配体-受体对，可能参与肺中的炎症和病原体清除。
