Assimilation of [57Co]-labeled cobalamin in human fetal gastrointestinal xenografts into nude mice.
Cobalamin (Cbl) and its Cbl-binding proteins are present in amniotic fluid. Because amniotic fluid is swallowed by the embryo-fetus, we studied the ability of Cbl to be transported and metabolized across the embryo-fetal digestive tract. Human embryonic stomachs and intestines were transplanted into nude mice. The basal secretion of Cbl-binding proteins was studied by gel filtration of the graft juices. Intrinsic factor (IF) was looked for in gastric mucosa by immunohistochemistry. The uptake of [57Co]-labeled Cbl by the intestinal graft was studied by Schilling tests and HPLC. IF, haptocorrin, and a transcobalamin-like protein were detected in gastric juice, with concentration ranges of 5.0-26.4, 1.9-27.1, and 5.2-12.6 pmol/mL, respectively. The IF [57Co]Cbl complex had a single isoprotein with a pI at 5.6, which was maintained after incubation with neuraminidase. Urine excretion percentages (Schilling tests) ranged from 5.5 to 21.2% and from 0.3 to 1.6% when cyano-[57Co]Cbl-IF or cyano-[57Co]Cbl, respectively, was instilled in intestinal grafts. Chloroquine reduced significantly the percentage of excreted [57Co]Cbl. The [57Co]Cbl was mainly excreted as cyano-[57Co]Cbl in urines, showing a low coenzyme conversion. In conclusion, IF is secreted by the nonstimulated embryonic stomach and lacks sialic acid. Cbl binds to it and is subsequently transported across the xenografted embryo-fetal intestine. This suggests that amniotic fluid may contribute to Cbl delivery to the embryo-fetus.
Aimone-Gastin
I
I
Cellular and Molecular Pathology in Nutrition, Faculté de Médecine de Nancy, Université H. Poincaré, Vandoeuvre lès Nancy, France.
Gueant
J L
JL
Plenat
F
F
Muhale
F
F
Maury
F
F
Djalali
M
M
Gerard
P
P
Duprez
A
A
D000653:Amniotic Fluid / Q000378:metabolism; D000818:Animals; D001693:Biological Transport, Active; D002352:Carrier Proteins / Q000378:metabolism; D003037:Cobalt Radioisotopes; D004064:Digestive System / Q000196:embryology / Q000378:metabolism*; D005260:Female; D006801:Humans; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000637:transplantation*; D007437:Intrinsic Factor / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D011247:Pregnancy; D013270:Stomach / Q000637:transplantation*; D014183:Transplantation, Heterologous; D014805:Vitamin B 12 / Q000378:metabolism* / Q000493:pharmacokinetics
D002352:Carrier Proteins; D003037:Cobalt Radioisotopes; D007437:Intrinsic Factor; D014805:Vitamin B 12