Folate Receptor β Regulates Integrin CD11b/CD18 Adhesion of a Macrophage Subset to Collagen

J Immunol. 2016 Sep 15;197(6):2229-38. doi: 10.4049/jimmunol.1501878. Epub 2016 Aug 17.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD11b Antigen / physiology*
  • CD18 Antigens / physiology*
  • Cell Adhesion
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Collagen / pharmacology*
  • Folate Receptor 2 / physiology*
  • Folic Acid / metabolism
  • Humans
  • Macrophages / physiology*
  • Tetradecanoylphorbol Acetate / pharmacology


  • CD11b Antigen
  • CD18 Antigens
  • Folate Receptor 2
  • ITGAM protein, human
  • Collagen
  • Folic Acid
  • Tetradecanoylphorbol Acetate