Pathways for the regulation of body iron homeostasis in response to experimental iron overload.
OBJECTIVE
Secondary iron overload is a frequent clinical condition found in association with multiple blood transfusions.


METHODS
To gain insight into adaptive changes in the expression of iron genes in duodenum, liver and spleen upon experimental iron overload we studied C57BL/6 mice receiving repetitive daily injections of iron-dextran for up to 5 days.


RESULTS
Iron initially accumulated in spleen macrophages but with subsequent increase in macrophage ferroportin and ferritin expression its content in the spleen decreased while a progressive storage of iron occurred within hepatocytes which was paralleled by a significant increase in hepcidin and hemojuvelin expression. Under these conditions, iron was still absorbed from the duodenal lumen as divalent metal transporter-1 expressions were high, however, most of the absorbed iron was incorporated into duodenal ferritin, while ferroportin expression drastically decreased and iron transfer to the circulation was reduced.


CONCLUSIONS
Experimental iron overload results in iron accumulation in macrophages and later in hepatocytes. In parallel, the transfer of iron from the gut to the circulation is diminished which may be referred to interference of hepcidin with ferroportin mediated iron export, thus preventing body iron accumulation.
Theurl
Igor
I
Department of General Internal Medicine, Clinical Immunology and Infectious Diseases, Medical University, Anichstr. 35, A-6020 Innsbruck, Austria.
Ludwiczek
Susanne
S
Eller
Philipp
P
Seifert
Markus
M
Artner
Erika
E
Brunner
Peter
P
Weiss
Günter
G
D000818:Animals; D017931:DNA Primers; D004195:Disease Models, Animal; D018450:Disease Progression; D004386:Duodenum / Q000378:metabolism; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology*; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics / Q000302:isolation & purification
D017931:DNA Primers; D012313:RNA; D007501:Iron