title: Leukocyte-associated Ig-like receptor-1 is a novel inhibitory receptor for surfactant protein D.
abstract: The collagenous C-type lectin, SP-D, is a multitrimeric glycoprotein present at mucosal surfaces and is involved in host defense against infections in mammals. SP-D has immunomodulatory properties, but the underlying mechanisms are incompletely understood. SP-D contains collagen domains. LAIR-1 is an inhibitory immune receptor at the cell surface of various immune-competent cells that binds collagen. We hypothesized that the immunomodulatory functions of SP-D can be mediated via interactions between its collagen domain and LAIR-1. Binding assays show that SP-D interacts via its collagenous domain with LAIR-1 and the related LAIR-2. This does not affect the mannan-binding capacities of SP-D, which induces cross-linking of LAIR-1 in a cellular reporter assay. Functional assays show that SP-D inhibits the production of FcαR-mediated reactive oxygen via LAIR-1. Our studies indicate that SP-D is a functional ligand of the immune inhibitory receptor LAIR-1. Thus, we have identified a novel pathway for the immunomodulatory functions of SP-D mediated via binding of its collagenous domains to LAIR-1. This may provide a mechanism for the unexplained immunomodulatory function of the collagenous domains of SP-D.
authors.affiliation: Laboratory of Translational Immunology, Department of Immunology, and.
authors.forename: Marloes J M
authors.initials: MJ
authors.lastname: Olde Nordkamp
authors.affiliation: Department of Infectious Diseases and Immunology, Division of Molecular Host Defence, Faculty of Veterinary Medicine, Utrecht University, the Netherlands; and.
authors.forename: Martin
authors.initials: M
authors.lastname: van Eijk
authors.affiliation: Department of Clinical Chemistry and Hematology, University Medical Centre Utrecht, the Netherlands;
authors.forename: Rolf T
authors.initials: RT
authors.lastname: Urbanus
authors.affiliation: Laboratory of Translational Immunology, Department of Immunology, and Department of Pediatrics, Wilhelmina Children's Hospital, Utrecht, the Netherlands.
authors.forename: Louis
authors.initials: L
authors.lastname: Bont
authors.affiliation: Department of Infectious Diseases and Immunology, Division of Molecular Host Defence, Faculty of Veterinary Medicine, Utrecht University, the Netherlands; and.
authors.forename: Henk P
authors.initials: HP
authors.lastname: Haagsman
authors.affiliation: Laboratory of Translational Immunology, Department of Immunology, and l.meyaard@umcutrecht.nl.
authors.forename: Linde
authors.initials: L
authors.lastname: Meyaard
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D037663:Pulmonary Surfactant-Associated Protein D / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011961:Receptors, Fc / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011971:Receptors, Immunologic / Q000819:agonists / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; C036832:Fc(alpha) receptor; C431503:LAIR-2 receptor; D037663:Pulmonary Surfactant-Associated Protein D; D011961:Receptors, Fc; D011971:Receptors, Immunologic; C108073:leukocyte-associated immunoglobulin-like receptor 1
keywords: LAIR-1; collectin; immunomodulatory; inhibitory immune receptor