Ferritin synthesis and Iron uptake in developing erythroid cells

The effect of maturation on ferritin synthesis and iron uptake by erythroid precursor cells was studied in vitro in rabbit bone marrow cells synchronized by actinomycin D. Early mononuclear precursors were compared with basophilic normoblasts and reticulocytes. Apoferritin synthesis was measured by following the incorporation of ³H‐amino acids into purified ferritin, and this was correlated with total protein synthesis and with radioactive iron uptake by whole cells and radioactive iron incorporation into heme and ferritin. With increasing cellular maturation, a progressive reduction in both apoferritin and total protein synthesis has been observed, undifferentiated cells synthesizing 12 times more protein and 20 times more ferritin than reticulocytes. The rate of ferritin synthesis was inversely related to the rate of radioactive iron uptake by whole cells and radioactive iron incorporation into heme; lowest rates of radioactive uptake and heme synthesis were found in undifferentiated cells, and highest rates in reticulocytes. Radioactive iron incorporation into ferritin was higher in basophilic normoblasts than in undifferentiated cells but was very low in reticulocytes. This sequence of events indicates that in developing erythroid cells the phase of maximal ferritin synthesis precedes the phase of maximal iron uptake. The accumulation of newly formed apoferritin is followed by an increase in cellular iron uptake and an increased retention of iron in ferritin. Finally, with continuing cellular maturation, ferritin iron and iron derived directly from transferrin are utilized for hemoglobin synthesis.