In vivo evidence for the functional heterogeneity of transferrin-bound iron. IV. Selective uptake by erythroid precursors of radioiron from portal vein plasma transferrin during intestinal iron absorption.

In addition to the previously demonstrated selective tissue uptake of iron from the two binding sites of transferrin, the Fletcher-Huehns hypothesis predicts that iron absorbed by the intestine is delivered selectively to the erythroblast-oriented iron-binding site of transferrin in portal plasma. We have tested this prediction in rats by measuring in vitro the rate and amount of radioiron taken up by reticulocytes and bone marrow erythroblasts from selectively labeled portal plasma and randomly labeled peripheral plasma. Portal plasma transferrin was significantly more effective than peripheral plasma in delivering radioiron to both reticulocytes and marrow erythroblasts; on a per-cell basis the erythroblasts took up about five times more radioiron. Iron-deficient reticulocytes were more avid but less discriminating than iron-replete reticulocytes in uptake of iron from the two plasma sources. When injected into normal test rats in vivo, radioiron from portal plasma was preferentially removed by red cell precursors and preferentially incorporated into heme extracted from marrow and spleen. These results support the concept of selective release of iron to erythroblast-oriented binding sites of portal plasma transferrin by intestinal cells during absorption. Combined with previously demonstrated selective tissue uptake of iron from transferrin, these experiments offer strong support for the active role of transferrin in the internal iron exchange of the rat.