title: Folate receptor-β constitutes a marker for human proinflammatory monocytes.
abstract: Activated macrophages are commonly involved in the pathogenesis of inflammatory and autoimmune diseases and have been frequently reported to overexpress FR-β. Although FR-targeted therapies aimed at eliminating activated macrophages have shown promise for treating inflammatory diseases, little work has been performed to evaluate whether other hematopoietic cells might also express FR-β. Analysis of peripheral blood cells with a mAb to human FR-β reveals that only monocytes express FR-β. Molecular characterization of these circulating monocytes further demonstrates that solely the classic/proinflammatory subset (CD14(high)CD16(-)) expresses the FR and that only CD14(high)CD16(-) FR-β(+) monocytes also display the ability to bind folate-linked molecules. Confirmation that this subset of monocytes indeed constitutes the proinflammatory subpopulation was obtained by demonstrating coexpression of FR-β with other proinflammatory markers, including CCR2 and HLA-DR. Synovial monocytes from the joints of patients with RA were also shown to express FR-β. As inhibition of the chemotaxis of proinflammatory monocytes into sites of inflammation has been explored frequently as a means of controlling autoimmune diseases, demonstration that FR-β is uniquely expressed on this proinflammatory subpopulation offers a new strategy to suppress migration of inflammatory monocytes into sites of inflammation.
authors.affiliation: Department of Chemistry, Purdue University, West Lafayette, Indiana, USA;
authors.forename: Jiayin
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Chemistry, Purdue University, West Lafayette, Indiana, USA;
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Hilgenbrink
authors.affiliation: Department of Chemistry, Purdue University, West Lafayette, Indiana, USA;
authors.forename: Wei
authors.initials: W
authors.lastname: Xia
authors.affiliation: Protein Interactions Group, Center for Cancer and Inflammation Program, National Cancer Institute-Frederick, National Institutes of Health, Frederick, Maryland, USA;
authors.forename: Yang
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Protein Interactions Group, Center for Cancer and Inflammation Program, National Cancer Institute-Frederick, National Institutes of Health, Frederick, Maryland, USA;
authors.forename: Dimiter S
authors.initials: DS
authors.lastname: Dimitrov
authors.affiliation: Department of Rheumatology, Clarian Arnett Health, Lafayette, Indiana, USA; and.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Lockwood
authors.affiliation: Department of Internal Medicine, Memorial Hermann Cancer Center, Division of Oncology, University of Texas Health Science Center at Houston, Medical School, Houston, Texas, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Amato
authors.affiliation: Department of Chemistry, Purdue University, West Lafayette, Indiana, USA; plow@purdue.edu.
authors.forename: Philip S
authors.initials: PS
authors.lastname: Low
mesh_terms: D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D058976:Folate Receptor 2 / Q000378:metabolism*; D006801:Humans; D016130:Immunophenotyping; D007167:Immunotherapy; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism*; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D010641:Phenotype; D013582:Synovial Fluid / Q000276:immunology / Q000378:metabolism
chemical_list: D015415:Biomarkers; D058976:Folate Receptor 2; D018950:Lipopolysaccharide Receptors
keywords: folate targeting; immunotherapy; inflammation; inflammatory subset