IRON RELEASE FROM HUMAN MONOCYTES AFTER ERYTHROPHAGOCYTOSIS IN-VITRO - AN INVESTIGATION IN NORMAL SUBJECTS AND HEREDITARY HEMOCHROMATOSIS PATIENTS

This study investigated the release of erythrocyte-derived iron from p urified human monocytes obtained from healthy volunteers and hereditar y hemochromatosis (HH) patients. After erythrophagocytosis of Fe-59-la beled erythrocytes, a complete transfer of iron from hemoglobin (Hb) t o ferritin was observed within 24 hours in both control and HH monocyt es. The iron was released from the monocytes in the form of ferritin, Hb, and as nonprotein bound low molecular weight iron (LMW-Fe), During the initial rapid phase (<1.5 hours), iron release mostly consisted o f Hb and LMW-Fe, while in the later phase (>1.5 hours), it was compose d of ferritin and LMW-Fe. The kinetics of iron release were identical for HH monocytes, A high percentage of the total amount of iron was re leased as Hb both by viable normal and HH monocytes, suggesting that i ron release as Hb is a physiologic process, which may occur whenever t he erythrocyte-processing capacity of macrophages is exceeded. Most re markably, HH monocytes released twice as much iron in a LMW form as co ntrol cells. Iron released in the form of LMW-Fe readily binds to plas ma transferrin and may contribute to the high transferrin saturation a nd the occurrence of circulating nontransferrin-bound iron observed in HH patients. (C) 1998 by The American Society of Hematology.