The high-affinity FBP/FR (folate-binding protein/folate receptor) is expressed in three isoforms. FRα and FRβ are attached to cell membranes by hydrophobic GPI (glycosylphosphatidylinositol) anchors, whereas FBPγ 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/FRα isoforms were established for the first time in human blood using antibodies specifically directed against human milk FBPα. The α isoforms identified on erythrocyte membranes, and in granulocytes and serum, only constituted an almost undetectable fraction of the functional FBP. The FBPα in neutrophil granulocytes was identified as a cytoplasmic component by indirect immunofluorescence. Gel filtration of serum revealed a peak of FBPα (>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.
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Research Article|
August 06 2008
α Isoforms of soluble and membrane-linked folate-binding protein in human blood
Mimi Høier-Madsen;
Mimi Høier-Madsen
*Department of Autoimmunology, Statens Serum Institut, Artillerivej 5, DK-2300, Copenhagen S, Denmark
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Jan Holm;
Jan Holm
†Department of Clinical Biochemistry, Nordsjællands Hospital – Hillerød, Helsevej 2, DK-3400, Hillerød, Denmark
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Steen I. Hansen
Steen I. Hansen
1
†Department of Clinical Biochemistry, Nordsjællands Hospital – Hillerød, Helsevej 2, DK-3400, Hillerød, Denmark
1To whom correspondence should be addressed ([email protected]).
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Publisher: Portland Press Ltd
Received:
October 10 2007
Revision Received:
June 23 2008
Accepted:
June 30 2008
Accepted Manuscript online:
June 30 2008
Online ISSN: 1573-4935
Print ISSN: 0144-8463
© The Authors Journal compilation © 2008 Biochemical Society
2008
Biosci Rep (2008) 28 (3): 153–160.
Article history
Received:
October 10 2007
Revision Received:
June 23 2008
Accepted:
June 30 2008
Accepted Manuscript online:
June 30 2008
Citation
Mimi Høier-Madsen, Jan Holm, Steen I. Hansen; α Isoforms of soluble and membrane-linked folate-binding protein in human blood. Biosci Rep 1 June 2008; 28 (3): 153–160. doi: https://doi.org/10.1042/BSR20070033
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