title: Characterization and developmental expression of binding sites for the transplacental iron transport protein, uteroferrin, in fetal hematopoietic tissues.
abstract: In the pig, iron transport to the developing fetus during pregnancy involves, in part, uteroferrin (UF), a secreted progesterone-induced protein of the uterus. Neonatal pigs suffer from anemia, and the decrease in the synthesis of UF protein in late pregnancy was suggested to be partly responsible for this condition. To examine whether diminished capacity for UF uptake by pig fetuses may also contribute to neonatal anemia, binding sites for 125I-UF were examined in plasma membrane-enriched fractions of fetal liver and spleen, which are sites of fetal hematopoiesis. In addition, changes in the number of these binding sites as a function of fetal development were evaluated. Binding of 125I-UF to liver membrane fractions was displaced by intact UF greater than deglycosylated (aglyco) UF greater than ovalbumin, but not by yeast mannan. Scatchard analysis of radioligand binding showed the presence of a single class of binding sites with a dissociation constant of 10(-7) M. During fetal development and at postpartum (day 5), liver binding sites for UF remained invariant and displayed the same affinity. In contrast, the number of binding sites for UF in fetal spleen increased from midpregnancy to parturition and remained elevated in day 5 neonatal spleen. Affinity cross-linking of 125I-UF to liver membrane-associated binding sites and subsequent analysis by gel electrophoresis and autoradiography demonstrated a single labeled protein complex of Mr 58,000 and 87,000 under denaturing and nondenaturing conditions, respectively. The appearance of these bands was inhibited by intact UF, but not ovalbumin. The characteristics of the membrane-associated binding sites for UF differed from those of the mannose-related receptor previously described in reticuloendothelial cells of fetal liver. The invariant presence of UF binding components in sites of hematopoiesis during fetal development suggests that mechanism(s) unrelated to specific uptake of UF are responsible for neonatal anemia.
authors.affiliation: Department of Animal Science, University of Florida, Gainesville 32611-0691.
authors.forename: F J
authors.initials: FJ
authors.lastname: Michel
authors.forename: M F
authors.initials: MF
authors.lastname: Fliss
authors.forename: F W
authors.initials: FW
authors.lastname: Bazer
authors.forename: R C
authors.initials: RC
authors.lastname: Simmen
mesh_terms: D000135:Acid Phosphatase; D000818:Animals; D000831:Animals, Newborn; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D003432:Cross-Linking Reagents; D005260:Female; D005333:Fetus / Q000378:metabolism*; D006413:Hematopoietic System / Q000196:embryology / Q000378:metabolism*; D007501:Iron / Q000737:chemistry / Q000378:metabolism*; D007527:Isoenzymes; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008667:Metalloproteins / Q000737:chemistry / Q000378:metabolism*; D010920:Placenta / Q000737:chemistry / Q000378:metabolism*; D011247:Pregnancy; D011485:Protein Binding; D013552:Swine; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D002352:Carrier Proteins; D003432:Cross-Linking Reagents; D007527:Isoenzymes; D008667:Metalloproteins; D007501:Iron; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase