TY - JOUR

T1 - alpha isoforms of soluble and membrane-linked folate-binding protein in human blood

AU - Hoier-Madsen, M.

AU - Holm, J.

AU - Hansen, S.I.

N1 - Times Cited: 0ArticleEnglishHansen, S. INordsjaellands Hosp Hillerod, Dept Clin Biochem, Helsevej 2, DK-3400 Hillerod, DenmarkCited References Count: 41348KEPORTLAND PRESS LTDTHIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLANDLONDON

PY - 2008

Y1 - 2008

N2 - Synopsis The high-affinity FBP/FR (folate-binding protein/folate receptor) is expressed in three isoforms. FR alpha and FR beta are attached to cell membranes by hydrophobic GPI (glycosyl phosphatidylinositol) anchors, whereas 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 established for the first time 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 FBP alpha in neutrophil granulocytes was identified as a cytoplasmic component by indirect immunofluorescence. Gel filtration of serum revealed a peak of FBP alpha (>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 Udgivelsesdato: 2008/6

AB - Synopsis The high-affinity FBP/FR (folate-binding protein/folate receptor) is expressed in three isoforms. FR alpha and FR beta are attached to cell membranes by hydrophobic GPI (glycosyl phosphatidylinositol) anchors, whereas 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 established for the first time 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 FBP alpha in neutrophil granulocytes was identified as a cytoplasmic component by indirect immunofluorescence. Gel filtration of serum revealed a peak of FBP alpha (>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 Udgivelsesdato: 2008/6

M3 - Journal article

VL - 28

SP - 153

EP - 160

JO - Bioscience Reports

JF - Bioscience Reports

SN - 0144-8463

IS - 3

ER -