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Blood, 15 May 2006, Vol. 107, No. 10, pp. 4142-4148. Prepublished online as a Blood First Edition Paper on January 24, 2006; DOI 10.1182/blood-2005-08-3364. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-08-3364v1 107/10/4142    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Theurl, I. Articles by Weiss, G. Search for Related Content PubMed PubMed Citation Articles by Theurl, I. Articles by Weiss, G. Related Collections Phagocytes Red Cells Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PHAGOCYTES Dysregulated monocyte iron homeostasis and erythropoietin formation in patients with anemia of chronic disease Igor Theurl, Verena Mattle, Markus Seifert, Mariagabriella Mariani, Christian Marth, and Günter Weiss From the Departments of General Internal Medicine and Obstetrics and Gynecology, Medical University, Innsbruck, Austria; and U.O. Ematologia 2, Ospedale Maggiore Policlinico, Milan, Italy. Anemia of chronic disease (ACD) is frequently found in patients with chronic immune activation. Since most studies on ACD pathophysiology were performed with cell culture or animal models but not in humans, we examined 37 ACD patients suffering from autoimmune diseases or infections, 10 subjects with iron-deficiency anemia (IDA), 10 anemic patients with hereditary spherocytosis (HS), and 27 age-matched controls. Although hemoglobin concentrations were comparable between ACD and IDA patients, the latter presented with significantly higher serum erythropoietin concentrations than ACD patients. The significant negative correlation between erythropoietin and hemoglobin levels observed in IDA patients was also found in a group of anemic but not hypoferremic hereditary spherocytosis subjects, but not in ACD patients. Increased serum concentrations of the hepcidin precursor prohepcidin were paralleled by a decreased expression of the iron exporter ferroportin in circulating monocytes of ACD patients. In the latter cells, increased amounts of the iron storage protein ferritin and a reduced activity of iron-regulatory protein indicated monocyte iron accumulation. Our data indicate that hypoferremia in ACD may result from downregulation of ferroportin expression by hepcidin and cytokines with subsequent iron retention in monocytes. Together with a diminished erythropoietin formation, the impaired iron recirculation from monocytes may be central in the pathophysiology of ACD in humans. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: I. Theurl, E. Aigner, M. Theurl, M. Nairz, M. Seifert, A. Schroll, T. Sonnweber, L. Eberwein, D. R. Witcher, A. T. Murphy, et al. Regulation of iron homeostasis in anemia of chronic disease and iron deficiency anemia: diagnostic and therapeutic implications Blood, May 21, 2009; 113(21): 5277 - 5286. [Abstract] [Full Text] [PDF] O. Kakhlon, H. Manning, W. Breuer, N. Melamed-Book, C. Lu, G. Cortopassi, A. Munnich, and Z. I. Cabantchik Cell functions impaired by frataxin deficiency are restored by drug-mediated iron relocation Blood, December 15, 2008; 112(13): 5219 - 5227. [Abstract] [Full Text] [PDF] G. Bergamaschi, K. Markopoulos, R. Albertini, A. Di Sabatino, F. Biagi, R. Ciccocioppo, E. Arbustini, and G. R. Corazza Anemia of chronic disease and defective erythropoietin production in patients with celiac disease Haematologica, December 1, 2008; 93(12): 1785 - 1791. [Abstract] [Full Text] [PDF] P. van der Meer, D. J. Lok, J. L. Januzzi, P. W. B.-A. de la Porte, E. Lipsic, J. van Wijngaarden, A. A. Voors, W. H. van Gilst, and D. J. van Veldhuisen Adequacy of endogenous erythropoietin levels and mortality in anaemic heart failure patients Eur. Heart J., June 2, 2008; 29(12): 1510 - 1515. [Abstract] [Full Text] [PDF] E. Aigner, I. Theurl, M. Theurl, D. Lederer, H. Haufe, O. Dietze, M. Strasser, C. Datz, and G. Weiss Pathways underlying iron accumulation in human nonalcoholic fatty liver disease Am. J. Clinical Nutrition, May 1, 2008; 87(5): 1374 - 1383. [Abstract] [Full Text] [PDF] I. Theurl, M. Theurl, M. Seifert, S. Mair, M. Nairz, H. Rumpold, H. Zoller, R. Bellmann-Weiler, H. Niederegger, H. Talasz, et al. Autocrine formation of hepcidin induces iron retention in human monocytes Blood, February 15, 2008; 111(4): 2392 - 2399. [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] Y.-S. Sohn, W. Breuer, A. Munnich, and Z. I. Cabantchik Redistribution of accumulated cell iron: a modality of chelation with therapeutic implications Blood, February 1, 2008; 111(3): 1690 - 1699. [Abstract] [Full Text] [PDF] J. l. Sullivan Macrophage Iron, Hepcidin, and Atherosclerotic Plaque Stability Experimental Biology and Medicine, September 1, 2007; 232(8): 1014 - 1020. [Abstract] [Full Text] [PDF] U. Merle, E. Fein, S. G. Gehrke, W. Stremmel, and H. Kulaksiz The Iron Regulatory Peptide Hepcidin Is Expressed in the Heart and Regulated by Hypoxia and Inflammation Endocrinology, June 1, 2007; 148(6): 2663 - 2668. [Abstract] [Full Text] [PDF] T. Ganz Molecular Control of Iron Transport J. Am. Soc. Nephrol., February 1, 2007; 18(2): 394 - 400. [Abstract] [Full Text] [PDF]

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