[Erythrophagocytosis and recycling of heme iron in normal and pathological conditions; regulation by hepcidin].
Most of the iron required for erythropoiesis is provided by heme iron recycling following degradation of senescent erythrocytes by tissue macrophages. Accumulation of biochemical modifications at the red blood cell membrane during ageing (externalisation of phosphatidyl-serine, peroxydation of membrane-bound lipoproteins, loss of sialic acid residues and formation of senescence neoantigens) constitute a series of signals that will allow the macrophage to identify the red blood cells to be eliminated, through interaction with specific receptors. After this initial recognition step, the red blood cell is internalised by phagocytosis, and phagosome maturation, which can comprise recruitment of the endoplasmic reticulum, will favour degradation of red blood cell constituents. Heme is catabolised by heme oxygenase 1, anchored in the endoplasmic reticulum membrane. A fraction of the released iron will be recycled back to the plasma through ferroportin, a membrane-bound Fe (II) export molecule, and a fraction will retained within the ferritin molecules, to be released at later stages. Multiple evidence coming from human diseases (type 4 hemochromatosis) and animal models indicate that ferroportin is essential for heme iron recycling by macrophages. Furthermore, ferroportin seems to be the molecular target of hepcidin, this circulating peptide synthesized by the liver and acting as a negative regulator of intestinal iron absorption and iron recycling by macrophages. Perturbations in erythrophagocytosis play a physiopathological role in several diseases, including hemochromatosis, anemia of chronic disorders and thalassemia.
Beaumont
C
C
Inserm U656, Faculté Xavier Bichat, Paris. beaumont@bichat.inserm.fr
Canonne-Hergaux
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F
D000740:Anemia / Q000097:blood; D023181:Antimicrobial Cationic Peptides / Q000502:physiology*; D027682:Cation Transport Proteins / Q000097:blood; D004905:Erythrocyte Aging; D004912:Erythrocytes / Q000737:chemistry*; D004920:Erythropoiesis; D005293:Ferritins / Q000097:blood; D006418:Heme / Q000378:metabolism*; D006432:Hemochromatosis / Q000097:blood; D022781:Hepatocytes / Q000378:metabolism; D064451:Hepcidins; D006801:Humans; D007249:Inflammation / Q000097:blood; D007408:Intestinal Absorption; D007501:Iron / Q000097:blood* / Q000493:pharmacokinetics; D008264:Macrophages / Q000502:physiology*; D008954:Models, Biological; D010587:Phagocytosis; D013789:Thalassemia / Q000097:blood; D000098742:Ferroportin
D023181:Antimicrobial Cationic Peptides; D027682:Cation Transport Proteins; C578702:HAMP protein, human; D064451:Hepcidins; D000098742:Ferroportin; D006418:Heme; D005293:Ferritins; D007501:Iron