Abstract
Folate, also known as vitamin B-9, 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) beta, a GPI-anchored protein belonging to the folate receptor family.
As FR beta 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 FR beta, 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 FR beta in the plasma membrane of human FR beta(+) macrophages and FR beta-transduced monocytic THP-1 cells.
In this manner, we identified a novel role of FR beta: that is, we report functional interactions of FR beta with receptors mediating cellular adhesion, in particular the CD11b/CD18 beta(2) integrin heterodimer complement receptor type 3/Mac-1. This interaction results in impeded adhesion of FR beta(+) human primary macrophages and THP-1 cells to collagen in comparison with their FR beta(-) counterparts.
We further show that FR beta is only expressed by human macrophages when differentiated with M-CSF. These findings thus identify FR beta as a novel CD11b/CD18 regulator for trafficking and homing of a subset of macrophages on collagen.