Anémie microcytaire hypochrome génétique par anomalies du métabolisme du fer
Carole BeaumontINSERM U773
Centre de Recherche Biomédicale Bichat BeaujonFaculté X. Bichat
Paris
Heme and iron recycling
20-25 mg Fe /day
Erythroblasts
Iron deficiency
Hypoxia
Stimulation of erythropoiesis(Anemia, Epo, bleeding,Hemolysis,dyserythropoiesis)
Hepcidin
Iron overload
inflammation
Regulation of hepcidin gene expression
BMPHemojuvelin
(HJV)
EP increases FPN and HO1 mRNA It is not an iron-mediated effect
Delaby et al., Biochem J 2008
In vitro erythrophagocytosis (cultured bone marrow-derived macrophages)
Heme-mediated transcriptional activation of FPN and HO-1
N
Fe
N
NN
CH3
CH3
CH3
CH3
PrPr
VI
VI
Erythrophagocytosis
Transcriptional activation
HO1 - FPN - Ferritin
Fe (II)
ProteinProtein
mRNAmRNA
Ferritin
Translational activation
Ferroportin Ferritin
Iron-dependant post-transcriptionalregulations (IRE/IRP)
Systemic signallingHepcidin
Marro et al., Haematologica 2010
Erythrophagocytosis in pathological conditions
Hemoglobinopathies
Spherocytosis, elliptocytosis,Gunther disease…
Plasmodium-infected erythrocytes
Iron-deficient erythrocytes
• Oxidative stress
• Increased productionof senescence antigens
• Activation of eryptosis
Reduced half-life of erythrocytes
Intravascular hemolysis ?
Increased erythrophagocytosis ?