α Isoforms of soluble and membrane-linked folate-binding protein in human blood

Abstract

The high-affinity FBP/FR (folate-binding protein/folate receptor) is expressed in three isoforms. FRa and FRβ are attached to cell membranes by hydrophobic GPI (glycosylphosphatidylinositol) anchors, whereas FBP? is a secretory protein. Mature neutrophil granulocytes contain a non-functional FRβ on the surface, and, in addition, nanomolar concentrations of a secretory functional FBP (29 kDa) can be present in the secondary granules. A statistically significant correlation between the concentrations of functional FBP, probably a γ isoform, in granulocytes and serum supported the hypothesis that serum FBP (29 kDa) mainly originates from neutrophils. The presence of FBP/FRa isoforms were established for the first time in human blood using antibodies specifically directed against human milk FBPa. The α isoforms identified on erythrocyte membranes, and in granulocytes and serum, only constituted an almost undetectable fraction of the functional FBP. The FBPa in neutrophil granulocytes was identified as a cytoplasmic component by indirect immunofluorescence. Gel filtration of serum revealed a peak of FBPa (>120 kDa), which could represent receptor fragments from decomposed erythrocytes and granulocytes. The soluble FBPs may exert bacteriostatic effects and protect folates in plasma from biological degradation, whereas FRs on the surface of blood cells could be involved in intracellular folate uptake or serve as signal proteins. The latter receptors have also been used for therapeutic targeting in malignancy. © 2008 Biochemical Society.