Changes in erythropoiesis in hereditary hemochromatosis are not mediated by HFE expression in nucleated red cells.
OBJECTIVE
The HFE protein interacts with the transferrin receptor (TfR) to regulate cellular iron uptake. Nucleated erythroid cells have the highest number of TfR and the greatest iron uptake. The aim of this study was to investigate whether erythroid iron uptake is directly affected by HFE mutations.


METHODS
Iron status and erythropoiesis was investigated in sixty, asymptomatic HFE C282Y homozygotes. Reverse transcription-polymerase chain reaction, flow cytometry and immunocytochemistry were employed to investigate the HFE expression profile of normal peripheral blood, nucleated erythroid cells and several cultured cell lines.


RESULTS
The HFE C282Y homozygous subjects showed subtle erythropoietic changes with raised transferrin saturation and reticulocyte counts and low-normal serum transferrin receptor levels, but normal erythrocyte count and mean cell volume. HFE mRNA was detected in macrophages and monocytes and HFE protein was detected in granulocytes and at low levels in monocytes. Cultured primary human erythroid colonies did not express HFE mRNA or protein.


CONCLUSIONS
There is evidence that HFE C282Y homozygotes display increased plasma iron turnover and increased erythropoiesis, despite there being no evidence that HFE is expressed in erythroid colonies with a normal HFE genotype. It is likely that HFE mutations do not directly alter erythroid iron handling, but alter the supply of iron to the erythroid tissues.
Feeney
Graham P
GP
Department of Haematology, University Hospital of Wales and University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, UK.
Carter
Kymberley
K
Masters
Gillian S
GS
Jackson
Helen A
HA
Cavil
Ivor
I
Worwood
Mark
M
D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology*; D004920:Erythropoiesis / Q000502:physiology*; D005260:Female; D005434:Flow Cytometry; D006432:Hemochromatosis / Q000235:genetics* / Q000378:metabolism*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000502:physiology*; D009000:Monocytes / Q000378:metabolism; D011990:Receptors, Transferrin / Q000097:blood
C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D011990:Receptors, Transferrin