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Identification of the haemoglobin scavenger receptor

Author

Listed:
  • Mette Kristiansen

    (Department of Medical Biochemistry)

  • Jonas H. Graversen

    (Department of Medical Biochemistry)

  • Christian Jacobsen

    (Department of Medical Biochemistry)

  • Ole Sonne

    (University of Aarhus)

  • Hans-Jürgen Hoffman

    (Department of Respiratory Diseases Aarhus University Hospital)

  • S.K. Alex Law

    (MRC Immunochemistry Unit, University of Oxford)

  • Søren K. Moestrup

    (Department of Medical Biochemistry)

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.

Suggested Citation

  • Mette Kristiansen & Jonas H. Graversen & Christian Jacobsen & Ole Sonne & Hans-Jürgen Hoffman & S.K. Alex Law & Søren K. Moestrup, 2001. "Identification of the haemoglobin scavenger receptor," Nature, Nature, vol. 409(6817), pages 198-201, January.
    • Handle: RePEc:nat:nature:v:409:y:2001:i:6817:d:10.1038_35051594
    DOI: 10.1038/35051594
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    Cited by:

    1. Magdalena Mierzchała-Pasierb & Małgorzata Lipińska-Gediga & Łukasz Lewandowski & Małgorzata Krzystek-Korpacka, 2023. "Alterations in Serum Concentration of Soluble CD163 within Five Study Days from ICU Admission Are Associated with In-Hospital Mortality of Septic Patients—A Preliminary Study," IJERPH, MDPI, vol. 20(3), pages 1-21, January.
    2. Eric D. Morrell & Sarah E. Holton & Matthew Lawrance & Marika Orlov & Zoie Franklin & Mallorie A. Mitchem & Hannah DeBerg & Vivian H. Gersuk & Ashley Garay & Elizabeth Barnes & Ted Liu & Ithan D. Pelt, 2023. "The transcriptional and phenotypic characteristics that define alveolar macrophage subsets in acute hypoxemic respiratory failure," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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