PMID- 16095591 OWN - NLM STAT- MEDLINE DCOM- 20051114 LR - 20161124 IS - 0014-4827 (Print) IS - 0014-4827 (Linking) VI - 310 IP - 1 DP - 2005 Oct 15 TI - A physiological model to study iron recycling in macrophages. PG - 43-53 AB - Following erythrophagocytosis (EP) of senescent red blood cells (RBCs), heme iron is recycled to the plasma by tissue macrophages. This process is critical for mammalian iron homeostasis but remains elusive. We characterized a cellular model using artificially-aged murine RBCs and murine bone marrow-derived macrophages (BMDMs) and study mRNA and protein expression of HO-1, ferroportin and ferritin after EP. In vitro ageing of RBCs was obtained by raising intracellular calcium concentration. These RBCs exhibit several features of erythrocyte senescence including externalization of phosphatidyl-serine, specific binding and phagocytosis by BMDMs. During the first hours of EP, we observed a rapid increase of HO-1 and ferroportin mRNAs and proteins, whereas ferritin protein expression was progressively induced with no major changes in RNA levels. At later stages after EP, a different pattern of expression was observed with a net decrease of ferroportin, a sustained high level of HO-1, and a strong increase in ferritins. Taken together, these results suggest that after EP, iron is rapidly extracted from heme and exported by ferroportin. Surprisingly, the gene expression profile at late stages after EP, which is indicative of iron storage, is reminiscent of what is observed in inflammation. However, phagocytosis of artificially-aged red blood cells seems to repress the proinflammatory response of macrophages. FAU - Delaby, Constance AU - Delaby C AD - Inserm U656, Fer et synthese d'heme, Genetique, Physiologie et Pathologie, Faculte de Medecine Xavier Bichat, 16, rue Henri Huchard, 75018 Paris, France. FAU - Pilard, Nathalie AU - Pilard N FAU - Hetet, Gilles AU - Hetet G FAU - Driss, Fathi AU - Driss F FAU - Grandchamp, Bernard AU - Grandchamp B FAU - Beaumont, Carole AU - Beaumont C FAU - Canonne-Hergaux, Francois AU - Canonne-Hergaux F LA - eng PT - Journal Article PL - United States TA - Exp Cell Res JT - Experimental cell research JID - 0373226 RN - 0 (Cation Transport Proteins) RN - 0 (Membrane Proteins) RN - 0 (RNA, Messenger) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (metal transporting protein 1) RN - 31C4KY9ESH (Nitric Oxide) RN - 9007-73-2 (Ferritins) RN - E1UOL152H7 (Iron) RN - EC 1.14.14.18 (Heme Oxygenase (Decyclizing)) RN - EC 1.14.14.18 (Heme Oxygenase-1) RN - EC 1.14.14.18 (Hmox1 protein, mouse) SB - IM MH - Animals MH - Blotting, Western MH - Cation Transport Proteins/biosynthesis/genetics MH - Erythrocytes/metabolism/physiology MH - Ferritins/genetics/metabolism MH - Fluorescent Antibody Technique MH - Heme Oxygenase (Decyclizing)/biosynthesis/genetics MH - Heme Oxygenase-1 MH - Inflammation MH - Iron/*metabolism MH - Macrophages/drug effects/metabolism/*physiology MH - Membrane Proteins MH - Mice MH - *Models, Biological MH - Nitric Oxide/metabolism MH - Phagocytosis/*physiology MH - RNA, Messenger/biosynthesis MH - Reverse Transcriptase Polymerase Chain Reaction MH - Tumor Necrosis Factor-alpha/metabolism EDAT- 2005/08/13 09:00 MHDA- 2005/11/15 09:00 CRDT- 2005/08/13 09:00 PHST- 2005/05/16 00:00 [received] PHST- 2005/07/01 00:00 [revised] PHST- 2005/07/05 00:00 [accepted] PHST- 2005/08/13 09:00 [pubmed] PHST- 2005/11/15 09:00 [medline] PHST- 2005/08/13 09:00 [entrez] AID - S0014-4827(05)00310-1 [pii] AID - 10.1016/j.yexcr.2005.07.002 [doi] PST - ppublish SO - Exp Cell Res. 2005 Oct 15;310(1):43-53. doi: 10.1016/j.yexcr.2005.07.002.