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Gene Review

CD163  -  CD163 molecule

Homo sapiens

Synonyms: Hemoglobin scavenger receptor, M130, MM130, Scavenger receptor cysteine-rich type 1 protein M130
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Disease relevance of CD163


Psychiatry related information on CD163


High impact information on CD163

  • Complexes of haemoglobin and multimeric haptoglobin (the 2-2 phenotype) exhibit higher functional affinity for CD 163 than do complexes of haemoglobin and dimeric haptoglobin (the 1-1 phenotype) [6].
  • CD163 mediates the internalization of hemoglobin-haptoglobin (Hb-Hp) complexes by macrophages [7].
  • Not only is Hb 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 [7].
  • Free Hb further induces heme oxygenase mRNA expression in CD163+ HEK293 cells, but not in CD163- cells [7].
  • However, in contrast to Hp, Hpr did not promote any high-affinity binding to the scavenger receptor CD163 [8].

Chemical compound and disease context of CD163

  • As hemoglobin can bind LPS and enhance its toxicity, it will be important to determine how cell surface and soluble CD163 influence inflammatory processes during sepsis [4].
  • The hemoglobin scavenger receptor (HbSR) CD163 is a monocyte/macrophage-specific glycoprotein that binds and facilitates uptake of haptoglobin-hemoglobin (Hp-Hb) complexes, which are rapidly formed in the circulation upon hemolysis of red blood cells [9].
  • Because opioid peptides might be of importance in inflammatory skin diseases, for example psoriasis, sections of skin from psoriatic patients were immunohistochemically stained with antisera against methionine and leucine enkephalin, CD68 (KP1, PG-M1), calprotectin (M747), M130 (Ber-MAC3), CD1a and CD3 [10].

Biological context of CD163

  • The mAb 2A10 recognizes a 120-kDa protein with sequence homology to the human CD163 and whose expression is restricted to the cells of the porcine monocyte/macrophage lineage [11].
  • Hemoglobin in plasma is instantly bound with high affinity to haptoglobin--an interaction leading to the recognition of the complex by HbSR/CD163 and endocytosis in macrophages [2].
  • The existence of several CD163 isoforms, which differ in the structure of their cytoplasmic domains and putative phosphorylation sites, suggests that these isoforms also differ in their signaling mechanism [12].
  • Endotoxin induces rapid metalloproteinase-mediated shedding followed by up-regulation of the monocyte hemoglobin scavenger receptor CD163 [4].
  • Cross-linking of CD163 on glucocorticoid-stimulated macrophages results in the secretion of several proinflammatory cytokines, but the precise mechanism of CD163 mediated signal transduction is not understood [12].

Anatomical context of CD163

  • Local production of sCD163 was evidenced by a 5-7-fold higher level of sCD163 in SF than in serum and by the correlation with synovial lining CD163+ macrophages in SpA [1].
  • All brightly CD14+ cells in or around vessel walls (interpreted as immigrant monocytes) were CD163+ [13].
  • RESULTS: CD163 was observed on all CD14+ cells in synovium and tonsil with the exception of cells within larger T lymphocyte clusters in synovium and within tonsillar follicles [13].
  • Macrophage subpopulations in rheumatoid synovium: reduced CD163 expression in CD4+ T lymphocyte-rich microenvironments [13].
  • Despite similar lymphocyte numbers, activated lymphocytes (CD69+) were significantly decreased in SpA versus RA patients, with an inverse correlation between CD163 and CD69 levels [1].

Associations of CD163 with chemical compounds

  • OBJECTIVE: The cell surface glycoprotein CD163 is a member of the cysteine-rich scavenger receptor family, highly specific for leukocytes of the mononuclear phagocyte lineage [13].
  • We found that in a dose-dependent manner soluble CD163 induces a decrease in CD69 expression, a reduced [(3)H]thymidine uptake and a down-regulated matrix metalloproteinase-9 RNA expression in phorbol myristate acetate-stimulated T-cells [14].
  • Cross-reactivity could be shown for anti-human CD14, CD163 and mannose receptor (CD206) mAbs [15].
  • Studies using the inhibitor TAPI-0 indicate that a metalloproteinase is responsible for LPS-mediated shedding of CD163 [4].
  • CD163 is a recently identified member of the scavenger receptor cysteine-rich superfamily, which is expressed on peripheral blood monocytes and most tissue macrophages and is thought to play an important role in the regulation of the inflammatory response of these cells [12].

Physical interactions of CD163

  • 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) [16].

Enzymatic interactions of CD163


Regulatory relationships of CD163

  • CD163 expression is significantly upregulated by glucocorticoids and IL-10 [17].
  • The protein products of the two different haptoglobin alleles differ in their ability to serve as an antioxidant against hemoglobin and also to activate the CD163 receptor [18].
  • However, not all CD163-positive cells expressed CCR2, which could be interpreted as a mechanism for retaining the macrophages in the skin [19].
  • De novo protein synthesis was not required for this inhibition, suggesting that TGF-beta regulates CD163 expression transcriptionally [20].
  • Concomitant treatment with IL-4/dexamethasone up-regulated significantly the expression of CD163 [21].

Other interactions of CD163

  • CONCLUSION: Within RA synovium, CD163 has major advantages as a macrophage marker and does not appear to be restricted to "mature" macrophages [13].
  • CD163: a signal receptor scavenging haptoglobin-hemoglobin complexes from plasma [16].
  • The clinical marker that was most associated with serum levels of soluble CD163 was levels of CRP [22].
  • The CD163 expression is induced by interleukin-6, interleukin-10 and glucocorticoids [16].
  • We conclude that CD163 has at least two distinct functions: the clearance of hemoglobin in its cell-bound form and participation in anti-inflammation as a soluble factor, exhibiting cytokine-like functions [14].

Analytical, diagnostic and therapeutic context of CD163


  1. Association of CD163+ macrophages and local production of soluble CD163 with decreased lymphocyte activation in spondylarthropathy synovitis. Baeten, D., Møller, H.J., Delanghe, J., Veys, E.M., Moestrup, S.K., De Keyser, F. Arthritis Rheum. (2004) [Pubmed]
  2. Haptoglobin and CD163: captor and receptor gating hemoglobin to macrophage lysosomes. Madsen, M., Graversen, J.H., Moestrup, S.K. Redox Rep. (2001) [Pubmed]
  3. CD163 identifies a unique population of ramified microglia in HIV encephalitis (HIVE). Roberts, E.S., Masliah, E., Fox, H.S. J. Neuropathol. Exp. Neurol. (2004) [Pubmed]
  4. Endotoxin induces rapid metalloproteinase-mediated shedding followed by up-regulation of the monocyte hemoglobin scavenger receptor CD163. Hintz, K.A., Rassias, A.J., Wardwell, K., Moss, M.L., Morganelli, P.M., Pioli, P.A., Givan, A.L., Wallace, P.K., Yeager, M.P., Guyre, P.M. J. Leukoc. Biol. (2002) [Pubmed]
  5. CD163, a marker of perivascular macrophages, is up-regulated by microglia in simian immunodeficiency virus encephalitis after haptoglobin-hemoglobin complex stimulation and is suggestive of breakdown of the blood-brain barrier. Borda, J.T., Alvarez, X., Mohan, M., Hasegawa, A., Bernardino, A., Jean, S., Aye, P., Lackner, A.A. Am. J. Pathol. (2008) [Pubmed]
  6. Identification of the haemoglobin scavenger receptor. Kristiansen, M., Graversen, J.H., Jacobsen, C., Sonne, O., Hoffman, H.J., Law, S.K., Moestrup, S.K. Nature (2001) [Pubmed]
  7. CD163 is the macrophage scavenger receptor for native and chemically modified hemoglobins in the absence of haptoglobin. Schaer, D.J., Schaer, C.A., Buehler, P.W., Boykins, R.A., Schoedon, G., Alayash, A.I., Schaffner, A. Blood (2006) [Pubmed]
  8. Haptoglobin-related protein is a high-affinity hemoglobin-binding plasma protein. Nielsen, M.J., Petersen, S.V., Jacobsen, C., Oxvig, C., Rees, D., M??ller, H.J., Moestrup, S.K. Blood (2006) [Pubmed]
  9. Pivotal advance: activation of cell surface Toll-like receptors causes shedding of the hemoglobin scavenger receptor CD163. Weaver, L.K., Hintz-Goldstein, K.A., Pioli, P.A., Wardwell, K., Qureshi, N., Vogel, S.N., Guyre, P.M. J. Leukoc. Biol. (2006) [Pubmed]
  10. Enkephalin-like immunoreactivity in human skin is found selectively in a fraction of CD68-positive dermal cells: increase in enkephalin-positive cells in lesional psoriasis. Nissen, J.B., Lund, M., Stengaard-Pedersen, K., Kragballe, K. Arch. Dermatol. Res. (1997) [Pubmed]
  11. The porcine 2A10 antigen is homologous to human CD163 and related to macrophage differentiation. Sánchez, C., Doménech, N., Vázquez, J., Alonso, F., Ezquerra, A., Domínguez, J. J. Immunol. (1999) [Pubmed]
  12. Interaction of CD163 with the regulatory subunit of casein kinase II (CKII) and dependence of CD163 signaling on CKII and protein kinase C. Ritter, M., Buechler, C., Kapinsky, M., Schmitz, G. Eur. J. Immunol. (2001) [Pubmed]
  13. Macrophage subpopulations in rheumatoid synovium: reduced CD163 expression in CD4+ T lymphocyte-rich microenvironments. Fonseca, J.E., Edwards, J.C., Blades, S., Goulding, N.J. Arthritis Rheum. (2002) [Pubmed]
  14. Only the soluble form of the scavenger receptor CD163 acts inhibitory on phorbol ester-activated T-lymphocytes, whereas membrane-bound protein has no effect. Frings, W., Dreier, J., Sorg, C. FEBS Lett. (2002) [Pubmed]
  15. Molecular cloning and characterization of markers and cytokines for equid myeloid cells. Steinbach, F., Stark, R., Ibrahim, S., Gawad, E.A., Ludwig, H., Walter, J., Commandeur, U., Mauel, S. Vet. Immunol. Immunopathol. (2005) [Pubmed]
  16. CD163: a signal receptor scavenging haptoglobin-hemoglobin complexes from plasma. Graversen, J.H., Madsen, M., Moestrup, S.K. Int. J. Biochem. Cell Biol. (2002) [Pubmed]
  17. Soluble CD163 inhibits phorbol ester-induced lymphocyte proliferation. Högger, P., Sorg, C. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  18. Intraplaque hemorrhage. Levy, A.P., Moreno, P.R. Curr. Mol. Med. (2006) [Pubmed]
  19. Expression of CCR2 on monocytes and macrophages in chronically inflamed skin in atopic dermatitis and psoriasis. Vestergaard, C., Just, H., Baumgartner Nielsen, J., Thestrup-Pedersen, K., Deleuran, M. Acta Derm. Venereol. (2004) [Pubmed]
  20. TGF-beta regulation of human macrophage scavenger receptor CD163 is Smad3-dependent. Pioli, P.A., Goonan, K.E., Wardwell, K., Guyre, P.M. J. Leukoc. Biol. (2004) [Pubmed]
  21. Serum of patients with Behçet's disease induces classical (pro-inflammatory) activation of human macrophages in vitro. Alpsoy, E., Kodelja, V., Goerdt, S., Orfanos, C.E., Zouboulis, C.h.C. Dermatology (Basel) (2003) [Pubmed]
  22. Elevated levels of soluble CD163 in sera and fluids from rheumatoid arthritis patients and inhibition of the shedding of CD163 by TIMP-3. Matsushita, N., Kashiwagi, M., Wait, R., Nagayoshi, R., Nakamura, M., Matsuda, T., Hogger, P., Guyre, P.M., Nagase, H., Matsuyama, T. Clin. Exp. Immunol. (2002) [Pubmed]
  23. Effects of antirheumatic treatments on the prostaglandin E2 biosynthetic pathway. Korotkova, M., Westman, M., Gheorghe, K.R., af Klint, E., Trollmo, C., Ulfgren, A.K., Klareskog, L., Jakobsson, P.J. Arthritis Rheum. (2005) [Pubmed]
  24. Development of an ELISA to measure soluble CD163 in biological fluids. Sulahian, T.H., Hintz, K.A., Wardwell, K., Guyre, P.M. J. Immunol. Methods (2001) [Pubmed]
  25. Hemoglobin scavenger receptor CD163 mediates interleukin-10 release and heme oxygenase-1 synthesis: antiinflammatory monocyte-macrophage responses in vitro, in resolving skin blisters in vivo, and after cardiopulmonary bypass surgery. Philippidis, P., Mason, J.C., Evans, B.J., Nadra, I., Taylor, K.M., Haskard, D.O., Landis, R.C. Circ. Res. (2004) [Pubmed]
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