Biology:CD163

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

CD163 (Cluster of Differentiation 163) is a protein that in humans is encoded by the CD163 gene.[1] CD163 is the high affinity scavenger receptor for the hemoglobin-haptoglobin complex[2] and in the absence of haptoglobin - with lower affinity - for hemoglobin alone.[3] It also is a marker of cells from the monocyte/macrophage lineage.[4] CD163 functions as innate immune sensor for gram-positive and gram-negative bacteria.[5][6] The receptor was discovered in 1987.[7]

Structure

The molecular size is 130 kDa. The receptor belongs to the scavenger receptor cysteine rich family type B and consists of a 1048 amino acid residues extracellular domain, a single transmembrane segment and a cytoplasmic tail with several splice variants.

Clinical significance

A soluble form of the receptor exists in plasma, and cerebrospinal fluid.,[8] commonly denoted sCD163. It is generated by ectodomain shedding of the membrane bound receptor, which may represent a form of modulation of CD163 function.[9] sCD163 shedding occurs as a result of enzymatic cleavage by ADAM17.[10] sCD163 is upregulated in a large range of inflammatory diseases including liver cirrhosis,[11] type 2 diabetes, macrophage activation syndrome, Gaucher's disease, sepsis, HIV infection, rheumatoid arthritis and Hodgkin Lymphoma.[12][13] sCD163 is also upregulated in cerebrospinal fluid after subarachnoid haemorrhage.[8] CD163 has recently been identified as expressed on neurons in the CNS following hemorrhage, although the significance of this is unclear.[14][15][16] The excretion of soluble CD163 into the urine is tightly associated with the presence of active glomerulonephritis in systemic lupus erythematosus and ANCA vasculitis and can be used to track response to therapy. [17]

Differences between mouse and human

Differences between mice and humans in CD163 biology are important to note since preclinical studies are frequently conducted in mice. sCD163 shedding occurs in humans but not mice, due to the emergence of an Arg-Ser-Ser-Arg sequence in humans, essential for enzymatic cleavage by ADAM17.[18] Human CD163, but not mouse CD163, exhibits a strikingly higher affinity to hemoglobin-haptoglobin complex compared to hemoglobin alone.[19]

Animal studies

Pigs with a section of the CD163 gene removed showed complete resistance to the virus that causes Porcine Reproductive and Respiratory Syndrome.[20]

Interactions

CD163 has been shown to interact with CSNK2B.[21]

See also

References

  1. ↑ "Entrez Gene: CD163 CD163 molecule". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9332. 
  2. ↑ "Identification of the haemoglobin scavenger receptor" (in En). Nature 409 (6817): 198–201. January 2001. doi:10.1038/35051594. PMID 11196644. Bibcode: 2001Natur.409..198K. 
  3. ↑ "CD163 is the macrophage scavenger receptor for native and chemically modified hemoglobins in the absence of haptoglobin". Blood 107 (1): 373–80. January 2006. doi:10.1182/blood-2005-03-1014. PMID 16189277. 
  4. ↑ "CD163: a specific marker of macrophages in paraffin-embedded tissue samples". American Journal of Clinical Pathology 122 (5): 794–801. November 2004. doi:10.1309/QHD6YFN81KQXUUH6. PMID 15491976. 
  5. ↑ "The macrophage scavenger receptor CD163 functions as an innate immune sensor for bacteria". Blood 113 (4): 887–92. January 2009. doi:10.1182/blood-2008-07-167064. PMID 18849484. https://pure.uva.nl/ws/files/1058309/145313_306960.pdf. 
  6. ↑ "Scavenger receptor CD163, a Jack-of-all-trades and potential target for cell-directed therapy". Molecular Immunology 47 (7–8): 1650–60. April 2010. doi:10.1016/j.molimm.2010.02.008. PMID 20299103. 
  7. ↑ "Scavenger receptor CD163 and its biological functions". Acta Medica 52 (2): 57–61. 2009. PMID 19777868. 
  8. ↑ 8.0 8.1 "The intrathecal CD163-haptoglobin-hemoglobin scavenging system in subarachnoid hemorrhage". Journal of Neurochemistry 121 (5): 785–92. June 2012. doi:10.1111/j.1471-4159.2012.07716.x. PMID 22380637. 
  9. ↑ "Shedding of CD163, a novel regulatory mechanism for a member of the scavenger receptor cysteine-rich family". Biochemical and Biophysical Research Communications 256 (1): 110–3. March 1999. doi:10.1006/bbrc.1999.0294. PMID 10066432. 
  10. ↑ "Tumor necrosis factor α-converting enzyme (TACE/ADAM17) mediates ectodomain shedding of the scavenger receptor CD163". Journal of Leukocyte Biology 88 (6): 1201–5. December 2010. doi:10.1189/jlb.0410235. PMID 20807704. 
  11. ↑ Tornai, Tamas; Vitalis, Zsuzsanna; Sipeki, Nora; Dinya, Tamas; Tornai, David; Antal‐Szalmas, Peter; Karanyi, Zsolt; Tornai, Istvan et al. (2016). "Macrophage activation marker, soluble CD163, is an independent predictor of short-term mortality in patients with cirrhosis and bacterial infection" (in en). Liver International 36 (11): 1628–1638. doi:10.1111/liv.13133. ISSN 1478-3231. PMID 27031405. https://onlinelibrary.wiley.com/doi/abs/10.1111/liv.13133. 
  12. ↑ "Serum CD163 and TARC as disease response biomarkers in classical Hodgkin lymphoma". Clinical Cancer Research 19 (3): 731–42. February 2013. doi:10.1158/1078-0432.CCR-12-2693. PMID 23224400. 
  13. ↑ "Soluble CD163". Scandinavian Journal of Clinical and Laboratory Investigation 72 (1): 1–13. February 2012. doi:10.3109/00365513.2011.626868. PMID 22060747. 
  14. ↑ "Hemoglobin-induced neuronal degeneration in the hippocampnus after neonatal intraventricular hemorrhage.". Brain Research 1635: 86–94. 15 March 2016. doi:10.1016/j.brainres.2015.12.060. PMID 26772987. 
  15. ↑ "CD163, a Hemoglobin/Haptoglobin Scavenger Receptor, After Intracerebral Hemorrhage: Functions in Microglia/Macrophages Versus Neurons.". Translational Stroke Research 8 (6): 612–616. April 6, 2017. doi:10.1007/s12975-017-0535-5. PMID 28386733. 
  16. ↑ "CD163 Expression in Neurons After Experimental Intracerebral Hemorrhage.". Stroke 48 (5): 1369–1375. May 1, 2017. doi:10.1161/STROKEAHA.117.016850. PMID 28360115. 
  17. ↑ O'Reilly, Vincent (September 2016). "Urinary Soluble CD163 in Active Renal Vasculitis". J Am Soc Nephrol 27 (9): 2906–2916. doi:10.1681/ASN.2015050511. PMID 26940094. PMC 5004645. https://jasn.asnjournals.org/content/27/9/2906.long. 
  18. ↑ "Structural basis for inflammation-driven shedding of CD163 ectodomain and tumor necrosis factor-α in macrophages". The Journal of Biological Chemistry 289 (2): 778–88. January 2014. doi:10.1074/jbc.m113.520213. PMID 24275664. 
  19. ↑ "Plasma clearance of hemoglobin and haptoglobin in mice and effect of CD163 gene targeting disruption". Antioxidants & Redox Signaling 18 (17): 2254–63. June 2013. doi:10.1089/ars.2012.4605. PMID 22793784. 
  20. ↑ "Precision engineering for PRRSV resistance in pigs: Macrophages from genome edited pigs lacking CD163 SRCR5 domain are fully resistant to both PRRSV genotypes while maintaining biological function". PLOS Pathogens 13 (2): e1006206. February 2017. doi:10.1371/journal.ppat.1006206. PMID 28231264. 
  21. ↑ "Interaction of CD163 with the regulatory subunit of casein kinase II (CKII) and dependence of CD163 signaling on CKII and protein kinase C". European Journal of Immunology 31 (4): 999–1009. April 2001. doi:10.1002/1521-4141(200104)31:4<999::AID-IMMU999>3.0.CO;2-R. PMID 11298324. 

Further reading

External links



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