title: CD163-L1 is an endocytic macrophage protein strongly regulated by mediators in the inflammatory response.
abstract: CD163-L1 belongs to the group B scavenger receptor cysteine-rich family of proteins, where the CD163-L1 gene arose by duplication of the gene encoding the hemoglobin scavenger receptor CD163 in late evolution. The current data demonstrate that CD163-L1 is highly expressed and colocalizes with CD163 on large subsets of macrophages, but in contrast to CD163 the expression is low or absent in monocytes and in alveolar macrophages, glia, and Kupffer cells. The expression of CD163-L1 increases when cultured monocytes are M-CSF stimulated to macrophages, and the expression is further increased by the acute-phase mediator IL-6 and the anti-inflammatory mediator IL-10 but is suppressed by the proinflammatory mediators IL-4, IL-13, TNF-α, and LPS/IFN-γ. Furthermore, we show that CD163-L1 is an endocytic receptor, which internalizes independently of cross-linking through a clathrin-mediated pathway. Two cytoplasmic splice variants of CD163-L1 are differentially expressed and have different subcellular distribution patterns. Despite its many similarities to CD163, CD163-L1 does not possess measurable affinity for CD163 ligands such as the haptoglobin-hemoglobin complex or various bacteria. In conclusion, CD163-L1 exhibits similarity to CD163 in terms of structure and regulated expression in cultured monocytes but shows clear differences compared with the known CD163 ligand preferences and expression pattern in the pool of tissue macrophages. We postulate that CD163-L1 functions as a scavenger receptor for one or several ligands that might have a role in resolution of inflammation.
authors.affiliation: Institute of Molecular Medicine, University of Southern Denmark, 5000 Odense, Denmark.
authors.forename: Jesper B
authors.initials: JB
authors.lastname: Moeller
authors.forename: Marianne J
authors.initials: MJ
authors.lastname: Nielsen
authors.forename: Martin P
authors.initials: MP
authors.lastname: Reichhardt
authors.forename: Anders
authors.initials: A
authors.lastname: Schlosser
authors.forename: Grith L
authors.initials: GL
authors.lastname: Sorensen
authors.forename: Ole
authors.initials: O
authors.lastname: Nielsen
authors.forename: Ida
authors.initials: I
authors.lastname: Tornøe
authors.forename: Jørn
authors.initials: J
authors.lastname: Grønlund
authors.forename: Maria E
authors.initials: ME
authors.lastname: Nielsen
authors.forename: Jan S
authors.initials: JS
authors.lastname: Jørgensen
authors.forename: Ole N
authors.initials: ON
authors.lastname: Jensen
authors.forename: Jan
authors.initials: J
authors.lastname: Mollenhauer
authors.forename: Søren K
authors.initials: SK
authors.lastname: Moestrup
authors.forename: Uffe
authors.initials: U
authors.lastname: Holmskov
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D004705:Endocytosis / Q000276:immunology*; D057809:HEK293 Cells; D018922:HL-60 Cells; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology*; D019169:Jurkat Cells; D007728:Kupffer Cells / Q000276:immunology / Q000473:pathology; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D016676:Macrophages, Alveolar / Q000276:immunology / Q000473:pathology; D051379:Mice; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009457:Neuroglia / Q000276:immunology / Q000473:pathology; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D020298:U937 Cells; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D018836:Inflammation Mediators; D011956:Receptors, Cell Surface