Identification of uteroglobin-related protein 1 and macrophage scavenger receptor with collagenous structure as a lung-specific ligand-receptor pair.
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.
Bin
Liang-Hua
LH
Department of Immunology, National Jewish Medical and Research Center, University of Colorado Health Sciences Center, Denver, CO 80206, USA.
Nielson
Larry D
LD
Liu
Xinqi
X
Mason
Robert J
RJ
Shu
Hong-Bing
HB
D000595:Amino Acid Sequence; D002352:Carrier Proteins; D002460:Cell Line; D003001:Cloning, Molecular; D003094:Collagen / Q000737:chemistry; D016207:Cytokines / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016147:Genes, Tumor Suppressor; D006801:Humans; D008024:Ligands; D008089:Listeria monocytogenes / Q000378:metabolism; D008168:Lung / Q000737:chemistry / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000378:metabolism; D008969:Molecular Sequence Data; D009928:Organ Specificity / Q000235:genetics; D011550:Pseudomonas aeruginosa / Q000378:metabolism; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051116:Receptors, Scavenger; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D060765:Secretoglobins; D014157:Transcription Factors / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D020298:U937 Cells; D014598:Uteroglobin
D002352:Carrier Proteins; D016207:Cytokines; D008024:Ligands; C490460:MARCO protein, human; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; C434732:SCGB3A1 protein, human; C449940:SCGB3A2 protein, human; D060765:Secretoglobins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D003094:Collagen; D014598:Uteroglobin