CD163: a signal receptor scavenging haptoglobin-hemoglobin complexes from plasma.
CD163 is a highly expressed macrophage membrane protein belonging to the scavenger receptor cysteine rich (SRCR) domain family. The CD163 expression is induced by interleukin-6, interleukin-10 and glucocorticoids. Its function has remained unknown until recently when CD163 was identified as the endocytic receptor binding hemoglobin (Hb) in complex with the plasma protein haptoglobin (Hp). This specific receptor-ligand interaction leading to removal from plasma of the Hp-Hb complex-but not free Hp or Hb-now explains the depletion of circulating Hp in individuals with increased intravascular hemolysis. Besides having a detoxificating effect by removing Hb from plasma, the CD163-mediated endocytosis of the Hp-Hb complex may represent a major pathway for uptake of iron in the tissue macrophages. The novel functional linkage of CD163 and Hp, which both are induced during inflammation, also reveal some interesting perspectives relating to the suggested anti-inflammatory properties of the receptor and the Hp phenotypes.
Graversen
Jonas Heilskov
JH
Department of Medical Biochemistry, University of Aarhus, Ole Worms Alle, Building 170, 8000 Aarhus C, Denmark.
Madsen
Mette
M
Moestrup
Søren K
SK
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic / Q000737:chemistry / Q000378:metabolism*; D018955:CD36 Antigens / Q000378:metabolism; D016384:Consensus Sequence; D017124:Conserved Sequence; D004705:Endocytosis; D006242:Haptoglobins / Q000378:metabolism*; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism*; D016415:Sequence Alignment; D015398:Signal Transduction; D000098902:CD163 Antigen
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D018955:CD36 Antigens; D006242:Haptoglobins; D006454:Hemoglobins; D046911:Macromolecular Substances; D011956:Receptors, Cell Surface