2. Academic Validation
  3. Folate receptor-β constitutes a marker for human proinflammatory monocytes

Folate receptor-β constitutes a marker for human proinflammatory monocytes

  • J Leukoc Biol. 2014 Oct;96(4):563-70. doi: 10.1189/jlb.2AB0713-372R.
Jiayin Shen 1,  Andrew R Hilgenbrink 1,  Wei Xia 1,  Yang Feng 2,  Dimiter S Dimitrov 2,  Michael B Lockwood 3,  Robert J Amato 4,  Philip S Low 5
Affiliations

Affiliations

  • 1 Department of Chemistry, Purdue University, West Lafayette, Indiana, USA;
  • 2 Protein Interactions Group, Center for Cancer and Inflammation Program, National Cancer Institute-Frederick, National Institutes of Health, Frederick, Maryland, USA;
  • 3 Department of Rheumatology, Clarian Arnett Health, Lafayette, Indiana, USA; and.
  • 4 Department of Internal Medicine, Memorial Hermann Cancer Center, Division of Oncology, University of Texas Health Science Center at Houston, Medical School, Houston, Texas, USA.
  • 5 Department of Chemistry, Purdue University, West Lafayette, Indiana, USA; plow@purdue.edu.
PMID: 25015955 DOI: 10.1189/jlb.2AB0713-372R
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.

Keywords

folate targeting; immunotherapy; inflammation; inflammatory subset.

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