Alpha–isoforms of soluble and membrane-linked folate binding protein in human blood

Mimi Høier-Madsen , Jan Holm , Steen Ingemann Hansen (1)

1 Department of Clinical Biochemistry

The high affinity folate binding protein/ folate receptor (FBP/FR) is expressed in three isoforms. FR alpha and beta are attached to cell membranes by hydrophobic glycosylphosphatidyl inositol (GPI) anchors, while FBP gamma is a secretory protein. Mature neutrophil granulocytes contain a non-functional FR beta 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 gamma isoform, in granulocytes and serum supported the hypothesis that serum FBP (29 kDa) mainly originates from neutrophils. The presence of FBP/FR alpha isoforms were for the first time established in human blood using antibodies specifically directed against human milk FBP alpha. The alpha isoforms identified on erythrocyte membranes, and in granulocytes and serum only constituted an almost undetectable fraction of the functional FBP. The alpha FBP in neutrophil granulocytes was identified as a cytoplasmic component by indirect immunofluorescence. Gel filtration of serum revealed a peak of alpha FBP (> 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, while 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.

Mots clés: Life Sciences

Mimi Høier-Madsen, Jan Holm, Steen Ingemann Hansen. Alpha–isoforms of soluble and membrane-linked folate binding protein in human blood. Bioscience Reports, 2008, 28 (3), pp.153-160. ⟨10.1042/BSR20070033⟩. ⟨hal-00479294⟩