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Blood, Vol. 92 No. 7 (October 1), 1998:
pp. 2511-2519
Iron Release From Human Monocytes After Erythrophagocytosis In
Vitro: An Investigation in Normal Subjects and Hereditary
Hemochromatosis Patients
Eunice Moura,
Minke A. Noordermeer,
Nanda Verhoeven,
Andreas F.M. Verheul, and
Joannes J.M. Marx
From the Department of Internal Medicine and Eijkman-Winkler
Institute for Microbiology, Infectious Diseases and Inflammation,
University Hospital Utrecht, Utrecht, The Netherlands; and Molecular
Pathology and Immunology, Abel Salazar Institute for the Biomedical
Sciences, Porto, Portugal.
This study investigated the release of erythrocyte-derived iron from
purified human monocytes obtained from healthy volunteers and
hereditary hemochromatosis (HH) patients. After erythrophagocytosis of
59Fe-labeled erythrocytes, a complete transfer of iron from
hemoglobin (Hb) to ferritin was observed within 24 hours in both
control and HH monocytes. 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 of Hb and LMW-Fe, while in the later phase
(>1.5 hours), it was composed 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 released as Hb both by viable normal and HH
monocytes, suggesting that iron release as Hb is a physiologic process,
which may occur whenever the erythrocyte-processing capacity of
macrophages is exceeded. Most remarkably, HH monocytes released twice
as much iron in a LMW form as control cells. Iron released in the form
of LMW-Fe readily binds to plasma transferrin and may contribute to the
high transferrin saturation and the occurrence of circulating
nontransferrin-bound iron observed in HH patients.
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