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Blood, 1 January 2006, Vol. 107, No. 1, pp. 373-380. Prepublished online as a Blood First Edition Paper on September 27, 2005; DOI 10.1182/blood-2005-03-1014. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: 2005-03-1014v1 107/1/373    most recent Alert me when this article is cited Alert me if a correction is posted 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 Schaer, D. J Articles by Schaffner, A. Search for Related Content PubMed PubMed Citation Articles by Schaer, D. J Articles by Schaffner, A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 14, 2005 Accepted August 20, 2005 CD163 is the macrophage scavenger receptor for native and chemically modified hemoglobins in the absence of haptoglobin Dominik J Schaer*, Christian A Schaer, Paul W Buehler, Robert A Boykins, Gabriele Schoedon, Abdu I Alayash, and Andreas Schaffner Medical Clinic B Research Unit, University of Zurich, Zurich, Switzerland Laboratory of Biochemistry and Vascular Biology, Center for Biologics Evaluation and Research, Food and Drug Administration (FDA), Bethesda, Maryland, USA Laboratory of Biophysics, Center for Biologics Evaluation and Research, Food and Drug Administration (FDA), Bethesda, Maryland, USA * Corresponding author; email: dominik.schaer{at}usz.ch. CD163 mediates the internalization of hemoglobin-haptoglobin (Hb-Hp) complexes by macrophages. As Hp binding capacity is exhausted during severe hemolysis, an Hp-independent Hb-clearance pathway is presumed to exist. We demonstrate that Hb interacts efficiently with CD163 in the absence of Hp. Hb is not only internalized into an endosomal compartment by CD163, as a result of active receptor dependent endocytosis; it also inhibits the uptake of Hb-Hp complexes, suggesting a common receptor binding site. Free Hb further induces heme oxygenase mRNA expression in CD163-positive cells, but not in CD163-negative cells. Additional evidence for Hp-independent Hb-CD163 interaction is provided by the demonstration that CD163 mediates uptake of --DBBF cross-linked Hb, a chemically modified Hb, which forms minimal Hp-complexes. Moreover, certain modifications to Hb, such as polymerization or the addition of specific functional groups (3 lysyl residues) to the beta-Cys93, can either reduce or enhance this pathway of uptake. In human macrophages, Hp-complex formation critically enhances Hb uptake at low (1 µg/mL) but not at high ( >100 µg/mL) ligand concentrations, lending support for a concentration-dependent biphasic model of macrophage Hb-clearance. These results identify CD163 as a scavenger receptor for native Hb and small-molecular-weight Hb-based blood substitutes following Hp depletion. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. Yunoki, T. Naruko, R. Komatsu, S. Ehara, N. Shirai, K. Sugioka, M. Nakagawa, C. Kitabayashi, Y. Ikura, A. Itoh, et al. Enhanced expression of haemoglobin scavenger receptor in accumulated macrophages of culprit lesions in acute coronary syndromes Eur. Heart J., August 1, 2009; 30(15): 1844 - 1852. [Abstract] [Full Text] [PDF] M. J. Nielsen and S. K. 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