title: CD300c is an activating receptor expressed on human monocytes.
abstract: Human CD300 molecules comprise a family of receptors that regulate many immune cell processes. They are mostly expressed on myeloid cells, although expression of two members, CD300a and CD300c, has also been described on lymphocytes. However, due to the lack of specific antibodies that distinguish between these two receptors, it has been difficult to determine the expression pattern and function of CD300a and CD300c in primary cells. Here, we have identified a specific monoclonal antibody, clone TX45, that recognizes only CD300c and show that within freshly isolated blood leukocytes, monocytes are the only cells that express CD300c on the cell surface. In vitro differentiation experiments revealed that CD300c is differentially expressed on different monocyte-derived cells, including macrophages and dendritic cells. Furthermore, TLR ligands LPS and flagellin dynamically regulate the expression of CD300c. Cross-linking of this receptor with clone TX45 monoclonal antibody induced calcium mobilization, upregulation of the costimulatory molecule CD86 and the production of inflammatory cytokines. Importantly, LPS-mediated production of inflammatory cytokines by monocytes was further enhanced if CD300c was simultaneously engaged by the agonist antibody. Altogether, our results show that human CD300c is an activating receptor expressed on monocytes and that it has a potential role in inflammatory responses.
authors.affiliation: Laboratory of Molecular and Developmental Immunology, Division of Monoclonal Antibodies, Office of Biotechnology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
authors.forename: Venkateswara R
authors.initials: VR
authors.lastname: Simhadri
authors.forename: John L
authors.initials: JL
authors.lastname: Mariano
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Gil-Krzewska
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhou
authors.forename: Francisco
authors.initials: F
authors.lastname: Borrego
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051940:B7-2 Antigen / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D020013:Calcium Signaling; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D005408:Flagellin / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology*; D061251:Primary Cell Culture; D020239:Receptor Cross-Talk
chemical_list: D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D051940:B7-2 Antigen; D015415:Biomarkers; C444139:CD300C protein, human; C497964:CD86 protein, human; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D005408:Flagellin