[Erythrophagocytosis and recycling of heme iron in normal and pathological conditions; regulation by hepcidin].

Abstract

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.

• Authors: C Beaumont, F Canonne-Hergaux
• Journal: Transfusion clinique et biologique : journal de la Societe francaise de transfusion sanguine (Transfus Clin Biol) Vol. 12 Issue 2 Pg. 123-30 (Jun 2005) ISSN: 1246-7820 [Print] France
• Vernacular Title: Erythrophagocytose et recyclage du fer héminique dans les conditions normales et pathologiques; régulation par l'hepcidine.
• PMID: 15927501 (Publication Type: English Abstract, Journal Article, Review)

Chemical References

• Antimicrobial Cationic Peptides
• Cation Transport Proteins
• HAMP protein, human
• Hepcidins
• metal transporting protein 1
• Heme
• Ferritins
• Iron

Topics

• Anemia (blood)
• Antimicrobial Cationic Peptides (physiology)
• Cation Transport Proteins (blood)
• Erythrocyte Aging
• Erythrocytes (chemistry)
• Erythropoiesis
• Ferritins (blood)
• Heme (metabolism)
• Hemochromatosis (blood)
• Hepatocytes (metabolism)
• Hepcidins
• Humans
• Inflammation (blood)
• Intestinal Absorption
• Iron (blood, pharmacokinetics)
• Macrophages (physiology)
• Models, Biological
• Phagocytosis
• Thalassemia (blood)