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 haptoglobinâhaemoglobin complexes. CD163 binds only haptoglobin and haemoglobin in complex, which indicates the exposure of a receptor-binding neoepitope. The receptorâligand 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 haptoglobinâhaemoglobin complexes is measurable in cells transfected with CD163 complementary DNA and in CD163-expressing myelo-monocytic lymphoma cells.
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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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Kristiansen, M., Graversen, J., Jacobsen, C. et al. Identification of the haemoglobin scavenger receptor. Nature 409, 198â201 (2001). https://doi.org/10.1038/35051594
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DOI: https://doi.org/10.1038/35051594
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