alpha Isoforms of soluble and membrane-linked folate-binding protein in human blood.
The high-affinity FBP/FR (folate-binding protein/folate receptor) is expressed in three isoforms. FRalpha and FRbeta are attached to cell membranes by hydrophobic GPI (glycosylphosphatidylinositol) anchors, whereas FBPgamma is a secretory protein. Mature neutrophil granulocytes contain a non-functional FRbeta 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/FRalpha isoforms were established for the first time in human blood using antibodies specifically directed against human milk FBPalpha. The alpha isoforms identified on erythrocyte membranes, and in granulocytes and serum, only constituted an almost undetectable fraction of the functional FBP. The FBPalpha in neutrophil granulocytes was identified as a cytoplasmic component by indirect immunofluorescence. Gel filtration of serum revealed a peak of FBPalpha (>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.
Høier-Madsen
Mimi
M
Department of Autoimmunology, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark.
Holm
Jan
J
Hansen
Steen I
SI
D000818:Animals; D000918:Antibody Specificity; D002352:Carrier Proteins / Q000097:blood*; D002417:Cattle; D002850:Chromatography, Gel; D003593:Cytoplasm / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D004910:Erythrocyte Membrane / Q000737:chemistry*; D019084:Fluorescent Antibody Technique, Indirect; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000097:blood; D006801:Humans; D007962:Leukocytes / Q000737:chemistry; D008565:Membrane Proteins / Q000097:blood*; D008894:Milk Proteins / Q000276:immunology; D009504:Neutrophils / Q000737:chemistry*; D010949:Plasma; D020033:Protein Isoforms / Q000097:blood; D011956:Receptors, Cell Surface / Q000097:blood*; D012995:Solubility
D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D008565:Membrane Proteins; D008894:Milk Proteins; D020033:Protein Isoforms; D011956:Receptors, Cell Surface; D005492:Folic Acid