title: Folate Receptor β Regulates Integrin CD11b/CD18 Adhesion of a Macrophage Subset to Collagen.
abstract: Folate, also known as vitamin B9, is necessary for essential cellular functions such as DNA synthesis, repair, and methylation. It is supplied to the cell via several transporters and receptors, including folate receptor (FR) β, a GPI-anchored protein belonging to the folate receptor family. As FRβ shows a restricted expression to cells of myeloid origin and only a subset of activated macrophages and placental cells have been shown to express functional FRβ, it represents a promising target for future therapeutic strategies. In this study, we performed affinity purification and mass spectrometric analysis of the protein microenvironment of FRβ in the plasma membrane of human FRβ(+) macrophages and FRβ-transduced monocytic THP-1 cells. In this manner, we identified a novel role of FRβ: that is, we report functional interactions of FRβ with receptors mediating cellular adhesion, in particular the CD11b/CD18 β2 integrin heterodimer complement receptor type 3/Mac-1. This interaction results in impeded adhesion of FRβ(+) human primary macrophages and THP-1 cells to collagen in comparison with their FRβ(-) counterparts. We further show that FRβ is only expressed by human macrophages when differentiated with M-CSF. These findings thus identify FRβ as a novel CD11b/CD18 regulator for trafficking and homing of a subset of macrophages on collagen.
authors.affiliation: Institute for Hygiene and Applied Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria;
authors.forename: Christian
authors.initials: C
authors.lastname: Machacek
authors.affiliation: Institute for Hygiene and Applied Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria;
authors.forename: Verena
authors.identifier: 0000-0003-2831-600X
authors.initials: V
authors.lastname: Supper
authors.affiliation: Institute for Hygiene and Applied Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria; Laboratory of Molecular Immunology, Institute of Molecular Biology, Slovak Academy of Sciences, 845 51 Bratislava, Slovakia;
authors.forename: Vladimir
authors.initials: V
authors.lastname: Leksa
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine, Medical University of Vienna, 1090 Vienna, Austria;
authors.forename: Goran
authors.identifier: 0000-0003-1964-3965
authors.initials: G
authors.lastname: Mitulovic
authors.affiliation: Department of Surgery and Core Facility Flow Cytometry, Medical University of Vienna, 1090 Vienna, Austria; and.
authors.forename: Andreas
authors.identifier: 0000-0003-2657-6836
authors.initials: A
authors.lastname: Spittler
authors.affiliation: EXBIO Praha, 252 42 Vestec, Czech Republic.
authors.forename: Karel
authors.identifier: 0000-0003-4450-4625
authors.initials: K
authors.lastname: Drbal
authors.affiliation: EXBIO Praha, 252 42 Vestec, Czech Republic.
authors.forename: Miloslav
authors.initials: M
authors.lastname: Suchanek
authors.affiliation: Institute for Hygiene and Applied Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria; hannes.stockinger@meduniwien.ac.at anna.repic@meduniwien.ac.at.
authors.forename: Anna
authors.identifier: 0000-0002-8005-8522
authors.initials: A
authors.lastname: Ohradanova-Repic
authors.affiliation: Institute for Hygiene and Applied Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria; hannes.stockinger@meduniwien.ac.at anna.repic@meduniwien.ac.at.
authors.forename: Hannes
authors.identifier: 0000-0001-6404-4430
authors.initials: H
authors.lastname: Stockinger
mesh_terms: D039481:CD11b Antigen / Q000502:physiology*; D018821:CD18 Antigens / Q000502:physiology*; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology*; D058976:Folate Receptor 2 / Q000502:physiology*; D005492:Folic Acid / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D039481:CD11b Antigen; D018821:CD18 Antigens; D058976:Folate Receptor 2; C509295:ITGAM protein, human; D003094:Collagen; D005492:Folic Acid; D013755:Tetradecanoylphorbol Acetate