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Blood, 1 October 2005, Vol. 106, No. 7, pp. 2572-2579. Prepublished online as a Blood First Edition Paper on June 9, 2005; DOI 10.1182/blood-2005-03-1185. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-03-1185v1 106/7/2572    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 Hvidberg, V. Articles by Moestrup, S. K. Search for Related Content PubMed PubMed Citation Articles by Hvidberg, V. Articles by Moestrup, S. K. Related Collections Phagocytes Red Cells Signal Transduction Free Research Articles Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Identification of the receptor scavenging hemopexin-heme complexes Vibeke Hvidberg, Maciej B. Maniecki, Christian Jacobsen, Peter Højrup, Holger J. Møller, and Søren K. Moestrup From the Department of Medical Biochemistry, University of Aarhus, Aarhus, Denmark; Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark; and Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark. Heme released from heme-binding proteins on internal hemorrhage, hemolysis, myolysis, or other cell damage is highly toxic due to oxidative and proinflammatory effects. Complex formation with hemopexin, the high-affinity heme-binding protein in plasma and cerebrospinal fluid, dampens these effects and is suggested to facilitate cellular heme metabolism. Using a ligand-affinity approach, we purified the human hemopexin-heme receptor and identified it as the low-density lipoprotein receptor-related protein (LRP)/CD91, a receptor expressed in several cell types including macrophages, hepatocytes, neurons, and syncytiotrophoblasts. Binding experiments, including Biacore analysis, showed that hemopexin-heme complex formation elicits the high receptor affinity. Uptake studies of radio-labeled hemopexin-heme complex in LRP/CD91-expressing COS cells and confocal microscopy of the cellular processing of fluorescent hemopexin-heme complex established the ability of LRP/CD91 to mediate hemopexin-heme internalization resulting in cellular heme uptake and lysosomal hemopexin degradation. Uptake of hemopexin-heme complex induced LRP/CD91-dependent heme-oxygenase 1 mRNA transcription in cultured monocytes. In conclusion, hemopexin-heme complexes are removed by a receptor-mediated pathway showing striking similarities to the CD163-mediated haptoglobin-hemoglobin clearance in macrophages. Furthermore, the data indicate a hitherto unknown role of LRP/CD91 in inflammation. (Blood. 2005; 106:2572-2579) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Handling heme Mitchell J. Weiss Blood 2005 106: 2225-2226. [Full Text] [PDF] This article has been cited by other articles: C. Heilmann, U. Geisen, C. Benk, M. Berchtold-Herz, G. Trummer, C. Schlensak, B. Zieger, and F. Beyersdorf Haemolysis in patients with ventricular assist devices: major differences between systems Eur. J. Cardiothorac. Surg., September 1, 2009; 36(3): 580 - 584. [Abstract] [Full Text] [PDF] X. Liang, T. Lin, G. Sun, L. Beasley-Topliffe, J.-M. Cavaillon, and H. S. Warren Hemopexin down-regulates LPS-induced proinflammatory cytokines from macrophages J. Leukoc. Biol., August 1, 2009; 86(2): 229 - 235. [Abstract] [Full Text] [PDF] M. J. Nielsen and S. K. Moestrup Receptor targeting of hemoglobin mediated by the haptoglobins: roles beyond heme scavenging Blood, July 23, 2009; 114(4): 764 - 771. [Abstract] [Full Text] [PDF] J. Watanabe, V. Grijalva, S. Hama, K. Barbour, F. G. Berger, M. Navab, A. M. Fogelman, and S. T. Reddy Hemoglobin and Its Scavenger Protein Haptoglobin Associate with ApoA-1-containing Particles and Influence the Inflammatory Properties and Function of High Density Lipoprotein J. Biol. Chem., July 3, 2009; 284(27): 18292 - 18301. [Abstract] [Full Text] [PDF] M. B. Maniecki, H. Hasle, L. Friis-Hansen, B. Lausen, O. J. Nielsen, K. Bendix, S. K. Moestrup, and H. J. Moller Impaired CD163-mediated hemoglobin-scavenging and severe toxic symptoms in patients treated with gemtuzumab ozogamicin Blood, August 15, 2008; 112(4): 1510 - 1514. [Abstract] [Full Text] [PDF] F. Vinchi, S. Gastaldi, L. Silengo, F. Altruda, and E. Tolosano Hemopexin Prevents Endothelial Damage and Liver Congestion in a Mouse Model of Heme Overload Am. J. Pathol., July 1, 2008; 173(1): 289 - 299. [Abstract] [Full Text] [PDF] I. Kimura, Y. Nakayama, H. Yamauchi, M. Konishi, A. Miyake, M. Mori, M. Ohta, N. Itoh, and M. Fujimoto Neurotrophic Activity of Neudesin, a Novel Extracellular Heme-binding Protein, Is Dependent on the Binding of Heme to Its Cytochrome b5-like Heme/Steroid-binding Domain J. Biol. Chem., February 15, 2008; 283(7): 4323 - 4331. [Abstract] [Full Text] [PDF] A. L. Lagan, D. D. Melley, T. W. Evans, and G. J. Quinlan Pathogenesis of the systemic inflammatory syndrome and acute lung injury: role of iron mobilization and decompartmentalization Am J Physiol Lung Cell Mol Physiol, February 1, 2008; 294(2): L161 - L174. [Abstract] [Full Text] [PDF] K. S. Lee, L. D. Raymond, B. Schoen, G. J. Raymond, L. Kett, R. A. Moore, L. M. Johnson, L. Taubner, J. O. Speare, H. A. Onwubiko, et al. Hemin Interactions and Alterations of the Subcellular Localization of Prion Protein J. Biol. Chem., December 14, 2007; 282(50): 36525 - 36533. [Abstract] [Full Text] [PDF] J. C. Mocny, J. S. Olson, and T. D. Connell Passively Released Heme from Hemoglobin and Myoglobin Is a Potential Source of Nutrient Iron for Bordetella bronchiseptica Infect. Immun., October 1, 2007; 75(10): 4857 - 4866. [Abstract] [Full Text] [PDF] J. Watanabe, K. J. Chou, J. C. Liao, Y. Miao, H.-H. Meng, H. Ge, V. Grijalva, S. Hama, K. Kozak, G. Buga, et al. 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