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Identification of the haemoglobin scavenger receptor

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Abstract

Intravascular haemolysis is a physiological phenomenon as well as a severe pathological complication when accelerated in various autoimmune, infectious (such as malaria) and inherited (such as sickle cell disease) disorders1. Haemoglobin released into plasma is captured by the acute phase protein haptoglobin, which is depleted from plasma during elevated haemolysis1. Here we report the identification of the acute phase-regulated and signal-inducing macrophage protein, CD163, as a receptor that scavenges haemoglobin by mediating endocytosis of haptoglobin–haemoglobin complexes. CD163 binds only haptoglobin and haemoglobin in complex, which indicates the exposure of a receptor-binding neoepitope. The receptor–ligand interaction is Ca2+-dependent and of high affinity. Complexes of haemoglobin and multimeric haptoglobin (the 2-2 phenotype) exhibit higher functional affinity for CD163 than do complexes of haemoglobin and dimeric haptoglobin (the 1-1 phenotype). Specific CD163-mediated endocytosis of haptoglobin–haemoglobin complexes is measurable in cells transfected with CD163 complementary DNA and in CD163-expressing myelo-monocytic lymphoma cells.

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Figure 1: Identification of CD163 as a binding protein of Hp–Hb.
Figure 2: Binding of Hp–Hb to CD163.
Figure 3: CD163-mediated endocytosis of 125I-labelled Hp–Hb.

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Acknowledgements

We thank K. Lassen and A.-M. Bundsgaard for technical assistance; K. Pulford for providing the SU-DHL-1 lymphoma cell line; and M. Sommerlund for inspiration.

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Author notes

  1. Mette Kristiansen, Jonas H. Graversen and S.K. Alex Law: These authors contributed equally to the work

Authors and Affiliations

  1. Department of Medical Biochemistry,

    Mette Kristiansen, Jonas H. Graversen, Christian Jacobsen & Søren K. Moestrup

  2. Department of Physiology, University of Aarhus, Ole Worms Alle, Aarhus C, 8000, Denmark

    Ole Sonne

  3. Department of Respiratory Diseases Aarhus University Hospital, Aarhus C, 8000, Denmark

    Hans-Jürgen Hoffman

  4. Department of Biochemistry, MRC Immunochemistry Unit, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK

    S.K. Alex Law

Authors
  1. Mette Kristiansen
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  4. Ole Sonne
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  7. Søren K. Moestrup
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Correspondence to Søren K. Moestrup.

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Kristiansen, M., Graversen, J., Jacobsen, C. et al. Identification of the haemoglobin scavenger receptor. Nature 409, 198–201 (2001). https://doi.org/10.1038/35051594

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