|
|
Blood, 1 December 2005, Vol. 106, No. 12, pp. 3979-3984.
Prepublished online as a Blood First Edition Paper on August 4, 2005; DOI 10.1182/blood-2005-06-2398.
Previous Article | Table of Contents | Next Article 
PHAGOCYTES
Presence of the iron exporter ferroportin at the plasma membrane of macrophages is enhanced by iron loading and down-regulated by hepcidin
Constance Delaby,
Nathalie Pilard,
Ana Sofia Gonçalves,
Carole Beaumont, and
François Canonne-Hergaux
From the Institut National de la Santé et de la Recherche Médicale (INSERM) U656, Fer et synthèse d'hème, Génétique, Physiologie et Pathologie, Faculté de médecine Xavier Bichat, Paris, France.
Ferroportin, the only mammalian iron exporter identified to date, is highly expressed in duodenal enterocytes and in macrophages. Several lines of evidence indicate that in enterocytes the iron export mediated by ferroportin occurs and is regulated at the basolateral cell surface, where the transporter is strongly expressed. By contrast, in macrophages, ferroportin has been shown in intracellular vesicles. We used a high-affinity antibody to specify the localization of endogenous ferroportin expressed in primary culture of bone marrowderived macrophages, in both basal and induced conditions. Our observations indicate that ferroportin is expressed in vesicular compartments that can reach the plasma membrane of macrophages. Of importance, when ferroportin expression was up-regulated through iron treatment or erythrophagocytosis, ferroportin expression was strongly enhanced at the plasma membrane of macrophages. Moreover, hepcidin dramatically reduced macrophage ferroportin protein levels. At the subcellular level, hepcidin was shown to induce rapid internalization and degradation of the macrophage iron exporter. These data are consistent with a direct iron export by ferroportin through the plasma membrane of macrophages and strongly support an efficient posttranscriptional down-regulation of ferroportin by hepcidin in these cells.

CiteULike Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
B. Chung, T. Chaston, J. Marks, S. K. Srai, and P. A. Sharp
Hepcidin Decreases Iron Transporter Expression in Vivo in Mouse Duodenum and Spleen and in Vitro in THP-1 Macrophages and Intestinal Caco-2 Cells
J. Nutr.,
August 1, 2009;
139(8):
1457 - 1462.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Robach, S. Recalcati, D. Girelli, C. Gelfi, N. J. Aachmann-Andersen, J. J. Thomsen, A. M. Norgaard, A. Alberghini, N. Campostrini, A. Castagna, et al.
Alterations of systemic and muscle iron metabolism in human subjects treated with low-dose recombinant erythropoietin
Blood,
June 25, 2009;
113(26):
6707 - 6715.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Matak, T. B. Chaston, B. Chung, S. K. Srai, A. T. McKie, and P. A. Sharp
Activated macrophages induce hepcidin expression in HuH7 hepatoma cells
Haematologica,
June 1, 2009;
94(6):
773 - 780.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
I. De Domenico, E. Lo, D. M. Ward, and J. Kaplan
Hepcidin-induced internalization of ferroportin requires binding and cooperative interaction with Jak2
PNAS,
March 10, 2009;
106(10):
3800 - 3805.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Iolascon, L. De Falco, and C. Beaumont
Molecular basis of inherited microcytic anemia due to defects in iron acquisition or heme synthesis
Haematologica,
March 1, 2009;
94(3):
395 - 408.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F. Aydemir, S. Jenkitkasemwong, S. Gulec, and M. D. Knutson
Iron Loading Increases Ferroportin Heterogeneous Nuclear RNA and mRNA Levels in Murine J774 Macrophages
J. Nutr.,
March 1, 2009;
139(3):
434 - 438.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. C. D'Anna, T. V. Veuthey, and M. E. Roque
Immunolocalization of Ferroportin in Healthy and Anemic Mice
J. Histochem. Cytochem.,
January 1, 2009;
57(1):
9 - 16.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. L. M. de Francisco, P. Stenvinkel, and S. Vaulont
Inflammation and its impact on anaemia in chronic kidney disease: from haemoglobin variability to hyporesponsiveness
NDT Plus,
January 1, 2009;
2(suppl_1):
i18 - i26.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. E. Van Zandt, F. B. Sow, W. C. Florence, B. S. Zwilling, A. R. Satoskar, L. S. Schlesinger, and W. P. Lafuse
The iron export protein ferroportin 1 is differentially expressed in mouse macrophage populations and is present in the mycobacterial-containing phagosome
J. Leukoc. Biol.,
September 1, 2008;
84(3):
689 - 700.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. N. Paradkar, I. De Domenico, N. Durchfort, I. Zohn, J. Kaplan, and D. M. Ward
Iron depletion limits intracellular bacterial growth in macrophages
Blood,
August 1, 2008;
112(3):
866 - 874.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Tacchini, E. Gammella, C. De Ponti, S. Recalcati, and G. Cairo
Role of HIF-1 and NF-{kappa}B Transcription Factors in the Modulation of Transferrin Receptor by Inflammatory and Anti-inflammatory Signals
J. Biol. Chem.,
July 25, 2008;
283(30):
20674 - 20686.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T Chaston, B Chung, M Mascarenhas, J Marks, B Patel, S K Srai, and P Sharp
Evidence for differential effects of hepcidin in macrophages and intestinal epithelial cells
Gut,
March 1, 2008;
57(3):
374 - 382.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. A. Schaer, F. Vallelian, A. Imhof, G. Schoedon, and D. J. Schaer
Heme carrier protein (HCP-1) spatially interacts with the CD163 hemoglobin uptake pathway and is a target of inflammatory macrophage activation
J. Leukoc. Biol.,
February 1, 2008;
83(2):
325 - 333.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. P. Mena, A. Esparza, V. Tapia, P. Valdes, and M. T. Nunez
Hepcidin inhibits apical iron uptake in intestinal cells
Am J Physiol Gastrointest Liver Physiol,
January 1, 2008;
294(1):
G192 - G198.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. D. Fleming
The Regulation of Hepcidin and Its Effects on Systemic and Cellular Iron Metabolism
Hematology,
January 1, 2008;
2008(1):
151 - 158.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. E. Techau, J. Valdez-Taubas, J.-F. Popoff, R. Francis, M. Seaman, and J. M. Blackwell
Evolution of Differences in Transport Function in Slc11a Family Members
J. Biol. Chem.,
December 7, 2007;
282(49):
35646 - 35656.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. T. Murphy, D. R. Witcher, P. Luan, and V. J. Wroblewski
Quantitation of hepcidin from human and mouse serum using liquid chromatography tandem mass spectrometry
Blood,
August 1, 2007;
110(3):
1048 - 1054.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
I. E. Zohn, I. De Domenico, A. Pollock, D. M. Ward, J. F. Goodman, X. Liang, A. J. Sanchez, L. Niswander, and J. Kaplan
The flatiron mutation in mouse ferroportin acts as a dominant negative to cause ferroportin disease
Blood,
May 15, 2007;
109(10):
4174 - 4180.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. Origa, R. Galanello, T. Ganz, N. Giagu, L. Maccioni, G. Faa, and E. Nemeth
Liver iron concentrations and urinary hepcidin in {beta}-thalassemia
Haematologica,
May 1, 2007;
92(5):
583 - 588.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
I. De Domenico, D. M. Ward, G. Musci, and J. Kaplan
Evidence for the multimeric structure of ferroportin
Blood,
March 1, 2007;
109(5):
2205 - 2209.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N.-B. Nguyen, K. D. Callaghan, A. J. Ghio, D. J. Haile, and F. Yang
Hepcidin expression and iron transport in alveolar macrophages
Am J Physiol Lung Cell Mol Physiol,
September 1, 2006;
291(3):
L417 - L425.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J.-C. Lesbordes-Brion, L. Viatte, M. Bennoun, D.-Q. Lou, G. Ramey, C. Houbron, G. Hamard, A. Kahn, and S. Vaulont
Targeted disruption of the hepcidin 1 gene results in severe hemochromatosis
Blood,
August 15, 2006;
108(4):
1402 - 1405.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. W. Swinkels, M. C.H. Janssen, J. Bergmans, and J. J.M. Marx
Hereditary Hemochromatosis: Genetic Complexity and New Diagnostic Approaches
Clin. Chem.,
June 1, 2006;
52(6):
950 - 968.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
I. Theurl, V. Mattle, M. Seifert, M. Mariani, C. Marth, and G. Weiss
Dysregulated monocyte iron homeostasis and erythropoietin formation in patients with anemia of chronic disease
Blood,
May 15, 2006;
107(10):
4142 - 4148.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Chlosta, D. S. Fishman, L. Harrington, E. E. Johnson, M. D. Knutson, M. Wessling-Resnick, and B. J. Cherayil
The Iron Efflux Protein Ferroportin Regulates the Intracellular Growth of Salmonella enterica.
Infect. Immun.,
May 1, 2006;
74(5):
3065 - 3067.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Viatte, G. Nicolas, D.-Q. Lou, M. Bennoun, J.-C. Lesbordes-Brion, F. Canonne-Hergaux, K. Schonig, H. Bujard, A. Kahn, N. C. Andrews, et al.
Chronic hepcidin induction causes hyposideremia and alters the pattern of cellular iron accumulation in hemochromatotic mice
Blood,
April 1, 2006;
107(7):
2952 - 2958.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|
|