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 ?