CD163: Difference between revisions

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{{Infobox_gene}}
{{Infobox_gene}}
'''CD163''' ('''C'''luster of '''D'''ifferentiation 163) is a [[protein]] that in humans is encoded by the CD163 [[gene]].<ref>{{cite web | title = Entrez Gene: CD163 CD163 molecule| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9332| accessdate = }}</ref> CD163 is the high affinity [[scavenger receptor (immunology)|scavenger receptor]] for the [[hemoglobin]]-[[haptoglobin]] complex and in the absence of haptoglobin - with lower affinity - for hemoglobin alone.<ref>CD163 is the macrophage scavenger receptor for native and chemically modified hemoglobins in the absence of haptoglobin.
'''CD163''' ('''C'''luster of '''D'''ifferentiation 163) is a [[protein]] that in humans is encoded by the CD163 [[gene]].<ref>{{cite web | title = Entrez Gene: CD163 CD163 molecule| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9332| access-date = }}</ref> CD163 is the high affinity [[scavenger receptor (immunology)|scavenger receptor]] for the [[hemoglobin]]-[[haptoglobin]] complex<ref>{{cite journal | vauthors = Kristiansen M, Graversen JH, Jacobsen C, Sonne O, Hoffman HJ, Law SK, Moestrup SK | title = Identification of the haemoglobin scavenger receptor | language = En | journal = Nature | volume = 409 | issue = 6817 | pages = 198–201 | date = January 2001 | pmid = 11196644 | doi = 10.1038/35051594 }}</ref> and in the absence of haptoglobin - with lower affinity - for hemoglobin alone.<ref name="pmid16189277">{{cite journal | vauthors = Schaer DJ, Schaer CA, Buehler PW, Boykins RA, Schoedon G, Alayash AI, Schaffner A | title = CD163 is the macrophage scavenger receptor for native and chemically modified hemoglobins in the absence of haptoglobin | journal = Blood | volume = 107 | issue = 1 | pages = 373–80 | date = January 2006 | pmid = 16189277 | doi = 10.1182/blood-2005-03-1014 }}</ref> It also is a [[Cluster of differentiation#Immunophenotyping|marker]] of cells from the [[monocyte]]/[[macrophage]] lineage.<ref>{{cite journal | vauthors = Lau SK, Chu PG, Weiss LM | title = CD163: a specific marker of macrophages in paraffin-embedded tissue samples | journal = American Journal of Clinical Pathology | volume = 122 | issue = 5 | pages = 794–801 | date = November 2004 | pmid = 15491976 | doi = 10.1309/QHD6YFN81KQXUUH6 }}</ref> CD163 functions as innate immune sensor for [[gram-positive]] and [[gram-negative]] bacteria.<ref name="PMID18849484">{{cite journal | vauthors = Fabriek BO, van Bruggen R, Deng DM, Ligtenberg AJ, Nazmi K, Schornagel K, Vloet RP, Dijkstra CD, van den Berg TK | title = The macrophage scavenger receptor CD163 functions as an innate immune sensor for bacteria | journal = Blood | volume = 113 | issue = 4 | pages = 887–92 | date = January 2009 | pmid = 18849484 | doi = 10.1182/blood-2008-07-167064 }}</ref><ref name="pmid20299103">{{cite journal | vauthors = Van Gorp H, Delputte PL, Nauwynck HJ | title = Scavenger receptor CD163, a Jack-of-all-trades and potential target for cell-directed therapy | journal = Molecular Immunology | volume = 47 | issue = 7-8 | pages = 1650–60 | date = April 2010 | pmid = 20299103 | doi = 10.1016/j.molimm.2010.02.008 }}</ref> The receptor was discovered in 1987.<ref name="pmid19777868">{{cite journal | vauthors = Onofre G, Kolácková M, Jankovicová K, Krejsek J | title = Scavenger receptor CD163 and its biological functions | journal = Acta Medica | volume = 52 | issue = 2 | pages = 57–61 | year = 2009 | pmid = 19777868 | doi =  }}</ref>
 
Schaer DJ, Schaer CA, Buehler PW, Boykins RA, Schoedon G, Alayash AI, Schaffner A.
 
Blood. 2006 Jan 1;107(1):373-80.
 
{{PMID|16189277}}
</ref> It has also been shown to mark cells of [[monocyte]]/[[macrophage]] lineage.<ref>{{cite journal | vauthors = Lau SK, Chu PG, Weiss LM | title = CD163: a specific marker of macrophages in paraffin-embedded tissues. | journal = Am. J. Clin. Path. | volume = 122 | issue = 5 | pages = 794–801 | year = 2004 | pmid = 15491976 | doi = 10.1309/QHD6YFN81KQXUUH6 }}</ref>
 
The receptor was discovered in 1987.<ref name="pmid19777868">{{cite journal | vauthors = Onofre G, Kolácková M, Jankovicová K, Krejsek J | title = Scavenger receptor CD163 and its biological functions | journal = Acta Medica (Hradec Kralove) | volume = 52 | issue = 2 | pages = 57–61 | year = 2009 | pmid = 19777868 | doi =  }}</ref>


== Structure ==
== Structure ==


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


A soluble form of the receptor exists in plasma, commonly denoted sCD163. It is generated by ectodomain shedding of the membrane bound receptor. sCD163 is upregulated in a large range of inflammatory diseases including liver cirrhosis, type 2 diabetes, [[macrophage activation syndrome]], [[Gaucher's disease]], [[sepsis]], HIV infection, rheumatoid arthritis and [[Hodgkin Lymphoma]].<ref name="pmid23224400">{{cite journal | vauthors = Jones K, Vari F, Keane C, Crooks P, Nourse JP, Seymour LA, Gottlieb D, Ritchie D, Gill D, Gandhi MK | title = Serum CD163 and TARC as disease response biomarkers in classical Hodgkin lymphoma | journal = Clin. Cancer Res. | volume = 19 | issue = 3 | pages = 731–42 | date = February 2013 | pmid = 23224400 | doi = 10.1158/1078-0432.CCR-12-2693 }}</ref><ref name="pmid22060747">{{cite journal | vauthors = Møller HJ | title = Soluble CD163 | journal = Scand. J. Clin. Lab. Invest. | volume = 72 | issue = 1 | pages = 1–13 | date = February 2012 | pmid = 22060747 | doi = 10.3109/00365513.2011.626868 }}</ref>
A soluble form of the receptor exists in plasma, and [[cerebrospinal fluid]].,<ref name=":0">{{cite journal | vauthors = Galea J, Cruickshank G, Teeling JL, Boche D, Garland P, Perry VH, Galea I | title = The intrathecal CD163-haptoglobin-hemoglobin scavenging system in subarachnoid hemorrhage | journal = Journal of Neurochemistry | volume = 121 | issue = 5 | pages = 785–92 | date = June 2012 | pmid = 22380637 | pmc = 3412209 | doi = 10.1111/j.1471-4159.2012.07716.x }}</ref> commonly denoted sCD163. It is generated by ectodomain shedding of the membrane bound receptor, which may represent a form of modulation of CD163 function.<ref>{{cite journal | vauthors = Droste A, Sorg C, Högger P | title = Shedding of CD163, a novel regulatory mechanism for a member of the scavenger receptor cysteine-rich family | journal = Biochemical and Biophysical Research Communications | volume = 256 | issue = 1 | pages = 110–3 | date = March 1999 | pmid = 10066432 | doi = 10.1006/bbrc.1999.0294 }}</ref> sCD163 shedding occurs as a result of enzymatic cleavage by ADAM17.<ref>{{cite journal | vauthors = Etzerodt A, Maniecki MB, Møller K, Møller HJ, Moestrup SK | title = Tumor necrosis factor α-converting enzyme (TACE/ADAM17) mediates ectodomain shedding of the scavenger receptor CD163 | journal = Journal of Leukocyte Biology | volume = 88 | issue = 6 | pages = 1201–5 | date = December 2010 | pmid = 20807704 | doi = 10.1189/jlb.0410235 }}</ref> sCD163 is upregulated in a large range of inflammatory diseases including liver [[cirrhosis]], type 2 [[Diabetes mellitus type 2|diabetes]], [[macrophage activation syndrome]], [[Gaucher's disease]], [[sepsis]], [[HIV]] infection, [[rheumatoid arthritis]] and [[Hodgkin Lymphoma]].<ref name="pmid23224400">{{cite journal | vauthors = Jones K, Vari F, Keane C, Crooks P, Nourse JP, Seymour LA, Gottlieb D, Ritchie D, Gill D, Gandhi MK | title = Serum CD163 and TARC as disease response biomarkers in classical Hodgkin lymphoma | journal = Clinical Cancer Research | volume = 19 | issue = 3 | pages = 731–42 | date = February 2013 | pmid = 23224400 | doi = 10.1158/1078-0432.CCR-12-2693 }}</ref><ref name="pmid22060747">{{cite journal | vauthors = Møller HJ | title = Soluble CD163 | journal = Scandinavian Journal of Clinical and Laboratory Investigation | volume = 72 | issue = 1 | pages = 1–13 | date = February 2012 | pmid = 22060747 | doi = 10.3109/00365513.2011.626868 }}</ref> sCD163 is also upregulated in cerebrospinal fluid after [[Subarachnoid hemorrhage|subarachnoid haemorrhage]].<ref name=":0" />
 
== 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]].<ref>{{cite journal | vauthors = Etzerodt A, Rasmussen MR, Svendsen P, Chalaris A, Schwarz J, Galea I, Møller HJ, Moestrup SK | title = Structural basis for inflammation-driven shedding of CD163 ectodomain and tumor necrosis factor-α in macrophages | journal = The Journal of Biological Chemistry | volume = 289 | issue = 2 | pages = 778–88 | date = January 2014 | pmid = 24275664 | doi = 10.1074/jbc.m113.520213 }}</ref> Human CD163, but mouse CD163, exhibits a strikingly higher affinity to [[hemoglobin]]-[[haptoglobin]] complex compared to hemoglobin alone.<ref>{{cite journal | vauthors = Etzerodt A, Kjolby M, Nielsen MJ, Maniecki M, Svendsen P, Moestrup SK | title = Plasma clearance of hemoglobin and haptoglobin in mice and effect of CD163 gene targeting disruption | journal = Antioxidants & Redox Signaling | volume = 18 | issue = 17 | pages = 2254–63 | date = June 2013 | pmid = 22793784 | doi = 10.1089/ars.2012.4605 }}</ref>


== Animal studies ==
== Animal studies ==


Pigs with a section of the CD163 gene removed showed complete resistance to the virus that causes [[Porcine reproductive and respiratory syndrome virus|Porcine Reproductive and Respiratory Syndrome]].<ref>{{cite journal | vauthors = Burkard C, Lillico SG, Reid E, Jackson B, Mileham AJ, Ait-Ali T, Whitelaw CB, Archibald AL | title = 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 | journal = PLoS Pathogens | volume = 13 | issue = 2 | pages = e1006206 | date = February 2017 | pmid = 28231264 | doi = 10.1371/journal.ppat.1006206 }}</ref>
Pigs with a section of the CD163 gene removed showed complete resistance to the virus that causes [[Porcine reproductive and respiratory syndrome virus|Porcine Reproductive and Respiratory Syndrome]].<ref>{{cite journal | vauthors = Burkard C, Lillico SG, Reid E, Jackson B, Mileham AJ, Ait-Ali T, Whitelaw CB, Archibald AL | title = 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 | journal = PLoS Pathogens | volume = 13 | issue = 2 | pages = e1006206 | date = February 2017 | pmid = 28231264 | pmc = 5322883 | doi = 10.1371/journal.ppat.1006206 }}</ref>


== Interactions ==
== Interactions ==


CD163 has been shown to [[Protein-protein interaction|interact]] with [[CSNK2B]].<ref name="pmid11298324">{{cite journal | vauthors = Ritter M, Buechler C, Kapinsky M, Schmitz G | title = Interaction of CD163 with the regulatory subunit of casein kinase II (CKII) and dependence of CD163 signaling on CKII and protein kinase C | journal = Eur. J. Immunol. | volume = 31 | issue = 4 | pages = 999–1009 | date = April 2001 | pmid = 11298324 | doi = 10.1002/1521-4141(200104)31:4<999::AID-IMMU999>3.0.CO;2-R }}</ref>
CD163 has been shown to [[Protein-protein interaction|interact]] with [[CSNK2B]].<ref name="pmid11298324">{{cite journal | vauthors = Ritter M, Buechler C, Kapinsky M, Schmitz G | title = Interaction of CD163 with the regulatory subunit of casein kinase II (CKII) and dependence of CD163 signaling on CKII and protein kinase C | journal = European Journal of Immunology | volume = 31 | issue = 4 | pages = 999–1009 | date = April 2001 | pmid = 11298324 | doi = 10.1002/1521-4141(200104)31:4<999::AID-IMMU999>3.0.CO;2-R }}</ref>
[[Chinese hamster ovary (CHO) cell]] or THP-1 transfer the CD163, can recognize the gram-positive and gram-negative bacterial.<ref name="PMID18849484">{{cite journal | vauthors = Fabriek BO, van Bruggen R, Deng DM, Ligtenberg AJ, Nazmi K, Schornagel K, Vloet RP, Dijkstra CD, van den Berg TK | title = The macrophage scavenger receptor CD163 functions as an innate immune sensor for bacteria. | journal = blood. | volume = 113 | issue = 4 | pages = 887–892 | date =January 2009  | pmid = 18849484 | doi =  10.1182/blood-2008-07-167064 }}</ref>


== See also ==
== See also ==
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== Further reading ==
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
* {{cite journal | vauthors = Graversen JH, Madsen M, Moestrup SK | title = CD163: a signal receptor scavenging haptoglobin-hemoglobin complexes from plasma. | journal = Int. J. Biochem. Cell Biol. | volume = 34 | issue = 4 | pages = 309–14 | year = 2002 | pmid = 11854028 | doi = 10.1016/S1357-2725(01)00144-3 }}
* {{cite journal | vauthors = Graversen JH, Madsen M, Moestrup SK | title = CD163: a signal receptor scavenging haptoglobin-hemoglobin complexes from plasma | journal = The International Journal of Biochemistry & Cell Biology | volume = 34 | issue = 4 | pages = 309–14 | date = April 2002 | pmid = 11854028 | doi = 10.1016/S1357-2725(01)00144-3 }}
* {{cite journal | vauthors = Madsen M, Graversen JH, Moestrup SK | title = Haptoglobin and CD163: captor and receptor gating hemoglobin to macrophage lysosomes. | journal = Redox Rep. | volume = 6 | issue = 6 | pages = 386–8 | year = 2002 | pmid = 11865982 | doi = 10.1179/135100001101536490 }}
* {{cite journal | vauthors = Madsen M, Graversen JH, Moestrup SK | title = Haptoglobin and CD163: captor and receptor gating hemoglobin to macrophage lysosomes | journal = Redox Report | volume = 6 | issue = 6 | pages = 386–8 | year = 2002 | pmid = 11865982 | doi = 10.1179/135100001101536490 }}
* {{cite journal | vauthors = Moestrup SK, Møller HJ | title = CD163: a regulated hemoglobin scavenger receptor with a role in the anti-inflammatory response. | journal = Ann. Med. | volume = 36 | issue = 5 | pages = 347–54 | year = 2005 | pmid = 15478309 | doi = 10.1080/07853890410033171 }}
* {{cite journal | vauthors = Moestrup SK, Møller HJ | title = CD163: a regulated hemoglobin scavenger receptor with a role in the anti-inflammatory response | journal = Annals of Medicine | volume = 36 | issue = 5 | pages = 347–54 | year = 2005 | pmid = 15478309 | doi = 10.1080/07853890410033171 }}
* {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. | journal = Gene | volume = 138 | issue = 1-2 | pages = 171–4 | year = 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
* {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1-2 | pages = 171–4 | date = January 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
* {{cite journal | vauthors = Law SK, Micklem KJ, Shaw JM, Zhang XP, Dong Y, Willis AC, Mason DY | title = A new macrophage differentiation antigen which is a member of the scavenger receptor superfamily. | journal = Eur. J. Immunol. | volume = 23 | issue = 9 | pages = 2320–5 | year = 1993 | pmid = 8370408 | doi = 10.1002/eji.1830230940 }}
* {{cite journal | vauthors = Law SK, Micklem KJ, Shaw JM, Zhang XP, Dong Y, Willis AC, Mason DY | title = A new macrophage differentiation antigen which is a member of the scavenger receptor superfamily | journal = European Journal of Immunology | volume = 23 | issue = 9 | pages = 2320–5 | date = September 1993 | pmid = 8370408 | doi = 10.1002/eji.1830230940 }}
* {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. | journal = Gene | volume = 200 | issue = 1-2 | pages = 149–56 | year = 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}
* {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1-2 | pages = 149–56 | date = October 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}
* {{cite journal | vauthors = Droste A, Sorg C, Högger P | title = Shedding of CD163, a novel regulatory mechanism for a member of the scavenger receptor cysteine-rich family. | journal = Biochem. Biophys. Res. Commun. | volume = 256 | issue = 1 | pages = 110–3 | year = 1999 | pmid = 10066432 | doi = 10.1006/bbrc.1999.0294 }}
* {{cite journal | vauthors = Droste A, Sorg C, Högger P | title = Shedding of CD163, a novel regulatory mechanism for a member of the scavenger receptor cysteine-rich family | journal = Biochemical and Biophysical Research Communications | volume = 256 | issue = 1 | pages = 110–3 | date = March 1999 | pmid = 10066432 | doi = 10.1006/bbrc.1999.0294 }}
* {{cite journal | vauthors = Ritter M, Buechler C, Langmann T, Schmitz G | title = Genomic organization and chromosomal localization of the human CD163 (M130) gene: a member of the scavenger receptor cysteine-rich superfamily. | journal = Biochem. Biophys. Res. Commun. | volume = 260 | issue = 2 | pages = 466–74 | year = 1999 | pmid = 10403791 | doi = 10.1006/bbrc.1999.0866 }}
* {{cite journal | vauthors = Ritter M, Buechler C, Langmann T, Schmitz G | title = Genomic organization and chromosomal localization of the human CD163 (M130) gene: a member of the scavenger receptor cysteine-rich superfamily | journal = Biochemical and Biophysical Research Communications | volume = 260 | issue = 2 | pages = 466–74 | date = July 1999 | pmid = 10403791 | doi = 10.1006/bbrc.1999.0866 }}
* {{cite journal | vauthors = Van den Heuvel MM, Tensen CP, van As JH, Van den Berg TK, Fluitsma DM, Dijkstra CD, Döpp EA, Droste A, Van Gaalen FA, Sorg C, Högger P, Beelen RH | title = Regulation of CD 163 on human macrophages: cross-linking of CD163 induces signaling and activation. | journal = J. Leukoc. Biol. | volume = 66 | issue = 5 | pages = 858–66 | year = 1999 | pmid = 10577520 | doi =  }}
* {{cite journal | vauthors = Van den Heuvel MM, Tensen CP, van As JH, Van den Berg TK, Fluitsma DM, Dijkstra CD, Döpp EA, Droste A, Van Gaalen FA, Sorg C, Högger P, Beelen RH | title = Regulation of CD 163 on human macrophages: cross-linking of CD163 induces signaling and activation | journal = Journal of Leukocyte Biology | volume = 66 | issue = 5 | pages = 858–66 | date = November 1999 | pmid = 10577520 | doi =  }}
* {{cite journal | vauthors = Buechler C, Ritter M, Orsó E, Langmann T, Klucken J, Schmitz G | title = Regulation of scavenger receptor CD163 expression in human monocytes and macrophages by pro- and antiinflammatory stimuli. | journal = J. Leukoc. Biol. | volume = 67 | issue = 1 | pages = 97–103 | year = 2000 | pmid = 10648003 | doi =  }}
* {{cite journal | vauthors = Buechler C, Ritter M, Orsó E, Langmann T, Klucken J, Schmitz G | title = Regulation of scavenger receptor CD163 expression in human monocytes and macrophages by pro- and antiinflammatory stimuli | journal = Journal of Leukocyte Biology | volume = 67 | issue = 1 | pages = 97–103 | date = January 2000 | pmid = 10648003 | doi =  }}
* {{cite journal | vauthors = Stover CM, Schleypen J, Grønlund J, Speicher MR, Schwaeble WJ, Holmskov U | title = Assignment of CD163B, the gene encoding M160, a novel scavenger receptor, to human chromosome 12p13.3 by in situ hybridization and somatic cell hybrid analysis. | journal = Cytogenet. Cell Genet. | volume = 90 | issue = 3-4 | pages = 246–7 | year = 2001 | pmid = 11124526 | doi = 10.1159/000056781 }}
* {{cite journal | vauthors = Stover CM, Schleypen J, Grønlund J, Speicher MR, Schwaeble WJ, Holmskov U | title = Assignment of CD163B, the gene encoding M160, a novel scavenger receptor, to human chromosome 12p13.3 by in situ hybridization and somatic cell hybrid analysis | journal = Cytogenetics and Cell Genetics | volume = 90 | issue = 3-4 | pages = 246–7 | year = 2001 | pmid = 11124526 | doi = 10.1159/000056781 }}
* {{cite journal | vauthors = Kristiansen M, Graversen JH, Jacobsen C, Sonne O, Hoffman HJ, Law SK, Moestrup SK | title = Identification of the haemoglobin scavenger receptor. | journal = Nature | volume = 409 | issue = 6817 | pages = 198–201 | year = 2001 | pmid = 11196644 | doi = 10.1038/35051594 }}
* {{cite journal | vauthors = Kristiansen M, Graversen JH, Jacobsen C, Sonne O, Hoffman HJ, Law SK, Moestrup SK | title = Identification of the haemoglobin scavenger receptor | journal = Nature | volume = 409 | issue = 6817 | pages = 198–201 | date = January 2001 | pmid = 11196644 | doi = 10.1038/35051594 }}
* {{cite journal | vauthors = Ritter M, Buechler C, Kapinsky M, Schmitz G | title = Interaction of CD163 with the regulatory subunit of casein kinase II (CKII) and dependence of CD163 signaling on CKII and protein kinase C. | journal = Eur. J. Immunol. | volume = 31 | issue = 4 | pages = 999–1009 | year = 2001 | pmid = 11298324 | doi = 10.1002/1521-4141(200104)31:4<999::AID-IMMU999>3.0.CO;2-R }}
* {{cite journal | vauthors = Ritter M, Buechler C, Kapinsky M, Schmitz G | title = Interaction of CD163 with the regulatory subunit of casein kinase II (CKII) and dependence of CD163 signaling on CKII and protein kinase C | journal = European Journal of Immunology | volume = 31 | issue = 4 | pages = 999–1009 | date = April 2001 | pmid = 11298324 | doi = 10.1002/1521-4141(200104)31:4<999::AID-IMMU999>3.0.CO;2-R }}
* {{cite journal | vauthors = Sulahian TH, Hintz KA, Wardwell K, Guyre PM | title = Development of an ELISA to measure soluble CD163 in biological fluids. | journal = J. Immunol. Methods | volume = 252 | issue = 1-2 | pages = 25–31 | year = 2001 | pmid = 11334962 | doi = 10.1016/S0022-1759(01)00328-3 }}
* {{cite journal | vauthors = Sulahian TH, Hintz KA, Wardwell K, Guyre PM | title = Development of an ELISA to measure soluble CD163 in biological fluids | journal = Journal of Immunological Methods | volume = 252 | issue = 1-2 | pages = 25–31 | date = June 2001 | pmid = 11334962 | doi = 10.1016/S0022-1759(01)00328-3 }}
* {{cite journal | vauthors = Högger P, Sorg C | title = Soluble CD163 inhibits phorbol ester-induced lymphocyte proliferation. | journal = Biochem. Biophys. Res. Commun. | volume = 288 | issue = 4 | pages = 841–3 | year = 2001 | pmid = 11688984 | doi = 10.1006/bbrc.2001.5845 }}
* {{cite journal | vauthors = Högger P, Sorg C | title = Soluble CD163 inhibits phorbol ester-induced lymphocyte proliferation | journal = Biochemical and Biophysical Research Communications | volume = 288 | issue = 4 | pages = 841–3 | date = November 2001 | pmid = 11688984 | doi = 10.1006/bbrc.2001.5845 }}
* {{cite journal | vauthors = Fonseca JE, Edwards JC, Blades S, Goulding NJ | title = Macrophage subpopulations in rheumatoid synovium: reduced CD163 expression in CD4+ T lymphocyte-rich microenvironments. | journal = Arthritis Rheum. | volume = 46 | issue = 5 | pages = 1210–6 | year = 2002 | pmid = 12115225 | doi = 10.1002/art.10207 }}
* {{cite journal | vauthors = Fonseca JE, Edwards JC, Blades S, Goulding NJ | title = Macrophage subpopulations in rheumatoid synovium: reduced CD163 expression in CD4+ T lymphocyte-rich microenvironments | journal = Arthritis and Rheumatism | volume = 46 | issue = 5 | pages = 1210–6 | date = May 2002 | pmid = 12115225 | doi = 10.1002/art.10207 }}
* {{cite journal | vauthors = Frings W, Dreier J, Sorg C | title = Only the soluble form of the scavenger receptor CD163 acts inhibitory on phorbol ester-activated T-lymphocytes, whereas membrane-bound protein has no effect. | journal = FEBS Lett. | volume = 526 | issue = 1-3 | pages = 93–6 | year = 2002 | pmid = 12208511 | doi = 10.1016/S0014-5793(02)03142-3 }}
* {{cite journal | vauthors = Frings W, Dreier J, Sorg C | title = Only the soluble form of the scavenger receptor CD163 acts inhibitory on phorbol ester-activated T-lymphocytes, whereas membrane-bound protein has no effect | journal = FEBS Letters | volume = 526 | issue = 1-3 | pages = 93–6 | date = August 2002 | pmid = 12208511 | doi = 10.1016/S0014-5793(02)03142-3 }}
* {{cite journal | vauthors = Matsushita N, Kashiwagi M, Wait R, Nagayoshi R, Nakamura M, Matsuda T, Hogger P, Guyre PM, Nagase H, Matsuyama T | title = Elevated levels of soluble CD163 in sera and fluids from rheumatoid arthritis patients and inhibition of the shedding of CD163 by TIMP-3. | journal = Clin. Exp. Immunol. | volume = 130 | issue = 1 | pages = 156–61 | year = 2002 | pmid = 12296867 | pmc = 1906487 | doi = 10.1046/j.1365-2249.2002.01963.x }}
* {{cite journal | vauthors = Matsushita N, Kashiwagi M, Wait R, Nagayoshi R, Nakamura M, Matsuda T, Hogger P, Guyre PM, Nagase H, Matsuyama T | title = Elevated levels of soluble CD163 in sera and fluids from rheumatoid arthritis patients and inhibition of the shedding of CD163 by TIMP-3 | journal = Clinical and Experimental Immunology | volume = 130 | issue = 1 | pages = 156–61 | date = October 2002 | pmid = 12296867 | pmc = 1906487 | doi = 10.1046/j.1365-2249.2002.01963.x }}
{{refend}}
{{refend}}



Latest revision as of 04:06, 22 August 2018

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
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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, type 2 diabetes, macrophage activation syndrome, Gaucher's disease, sepsis, HIV infection, rheumatoid arthritis and Hodgkin Lymphoma.[11][12] sCD163 is also upregulated in cerebrospinal fluid after subarachnoid haemorrhage.[8]

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.[13] Human CD163, but mouse CD163, exhibits a strikingly higher affinity to hemoglobin-haptoglobin complex compared to hemoglobin alone.[14]

Animal studies

Pigs with a section of the CD163 gene removed showed complete resistance to the virus that causes Porcine Reproductive and Respiratory Syndrome.[15]

Interactions

CD163 has been shown to interact with CSNK2B.[16]

See also

References

  1. "Entrez Gene: CD163 CD163 molecule".
  2. Kristiansen M, Graversen JH, Jacobsen C, Sonne O, Hoffman HJ, Law SK, Moestrup SK (January 2001). "Identification of the haemoglobin scavenger receptor". Nature. 409 (6817): 198–201. doi:10.1038/35051594. PMID 11196644.
  3. Schaer DJ, Schaer CA, Buehler PW, Boykins RA, Schoedon G, Alayash AI, Schaffner A (January 2006). "CD163 is the macrophage scavenger receptor for native and chemically modified hemoglobins in the absence of haptoglobin". Blood. 107 (1): 373–80. doi:10.1182/blood-2005-03-1014. PMID 16189277.
  4. Lau SK, Chu PG, Weiss LM (November 2004). "CD163: a specific marker of macrophages in paraffin-embedded tissue samples". American Journal of Clinical Pathology. 122 (5): 794–801. doi:10.1309/QHD6YFN81KQXUUH6. PMID 15491976.
  5. Fabriek BO, van Bruggen R, Deng DM, Ligtenberg AJ, Nazmi K, Schornagel K, Vloet RP, Dijkstra CD, van den Berg TK (January 2009). "The macrophage scavenger receptor CD163 functions as an innate immune sensor for bacteria". Blood. 113 (4): 887–92. doi:10.1182/blood-2008-07-167064. PMID 18849484.
  6. Van Gorp H, Delputte PL, Nauwynck HJ (April 2010). "Scavenger receptor CD163, a Jack-of-all-trades and potential target for cell-directed therapy". Molecular Immunology. 47 (7–8): 1650–60. doi:10.1016/j.molimm.2010.02.008. PMID 20299103.
  7. Onofre G, Kolácková M, Jankovicová K, Krejsek J (2009). "Scavenger receptor CD163 and its biological functions". Acta Medica. 52 (2): 57–61. PMID 19777868.
  8. 8.0 8.1 Galea J, Cruickshank G, Teeling JL, Boche D, Garland P, Perry VH, Galea I (June 2012). "The intrathecal CD163-haptoglobin-hemoglobin scavenging system in subarachnoid hemorrhage". Journal of Neurochemistry. 121 (5): 785–92. doi:10.1111/j.1471-4159.2012.07716.x. PMC 3412209. PMID 22380637.
  9. Droste A, Sorg C, Högger P (March 1999). "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. doi:10.1006/bbrc.1999.0294. PMID 10066432.
  10. Etzerodt A, Maniecki MB, Møller K, Møller HJ, Moestrup SK (December 2010). "Tumor necrosis factor α-converting enzyme (TACE/ADAM17) mediates ectodomain shedding of the scavenger receptor CD163". Journal of Leukocyte Biology. 88 (6): 1201–5. doi:10.1189/jlb.0410235. PMID 20807704.
  11. Jones K, Vari F, Keane C, Crooks P, Nourse JP, Seymour LA, Gottlieb D, Ritchie D, Gill D, Gandhi MK (February 2013). "Serum CD163 and TARC as disease response biomarkers in classical Hodgkin lymphoma". Clinical Cancer Research. 19 (3): 731–42. doi:10.1158/1078-0432.CCR-12-2693. PMID 23224400.
  12. Møller HJ (February 2012). "Soluble CD163". Scandinavian Journal of Clinical and Laboratory Investigation. 72 (1): 1–13. doi:10.3109/00365513.2011.626868. PMID 22060747.
  13. Etzerodt A, Rasmussen MR, Svendsen P, Chalaris A, Schwarz J, Galea I, Møller HJ, Moestrup SK (January 2014). "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. doi:10.1074/jbc.m113.520213. PMID 24275664.
  14. Etzerodt A, Kjolby M, Nielsen MJ, Maniecki M, Svendsen P, Moestrup SK (June 2013). "Plasma clearance of hemoglobin and haptoglobin in mice and effect of CD163 gene targeting disruption". Antioxidants & Redox Signaling. 18 (17): 2254–63. doi:10.1089/ars.2012.4605. PMID 22793784.
  15. Burkard C, Lillico SG, Reid E, Jackson B, Mileham AJ, Ait-Ali T, Whitelaw CB, Archibald AL (February 2017). "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. doi:10.1371/journal.ppat.1006206. PMC 5322883. PMID 28231264.
  16. Ritter M, Buechler C, Kapinsky M, Schmitz G (April 2001). "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. doi:10.1002/1521-4141(200104)31:4<999::AID-IMMU999>3.0.CO;2-R. PMID 11298324.

Further reading

  • Graversen JH, Madsen M, Moestrup SK (April 2002). "CD163: a signal receptor scavenging haptoglobin-hemoglobin complexes from plasma". The International Journal of Biochemistry & Cell Biology. 34 (4): 309–14. doi:10.1016/S1357-2725(01)00144-3. PMID 11854028.
  • Madsen M, Graversen JH, Moestrup SK (2002). "Haptoglobin and CD163: captor and receptor gating hemoglobin to macrophage lysosomes". Redox Report. 6 (6): 386–8. doi:10.1179/135100001101536490. PMID 11865982.
  • Moestrup SK, Møller HJ (2005). "CD163: a regulated hemoglobin scavenger receptor with a role in the anti-inflammatory response". Annals of Medicine. 36 (5): 347–54. doi:10.1080/07853890410033171. PMID 15478309.
  • Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
  • Law SK, Micklem KJ, Shaw JM, Zhang XP, Dong Y, Willis AC, Mason DY (September 1993). "A new macrophage differentiation antigen which is a member of the scavenger receptor superfamily". European Journal of Immunology. 23 (9): 2320–5. doi:10.1002/eji.1830230940. PMID 8370408.
  • Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
  • Droste A, Sorg C, Högger P (March 1999). "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. doi:10.1006/bbrc.1999.0294. PMID 10066432.
  • Ritter M, Buechler C, Langmann T, Schmitz G (July 1999). "Genomic organization and chromosomal localization of the human CD163 (M130) gene: a member of the scavenger receptor cysteine-rich superfamily". Biochemical and Biophysical Research Communications. 260 (2): 466–74. doi:10.1006/bbrc.1999.0866. PMID 10403791.
  • Van den Heuvel MM, Tensen CP, van As JH, Van den Berg TK, Fluitsma DM, Dijkstra CD, Döpp EA, Droste A, Van Gaalen FA, Sorg C, Högger P, Beelen RH (November 1999). "Regulation of CD 163 on human macrophages: cross-linking of CD163 induces signaling and activation". Journal of Leukocyte Biology. 66 (5): 858–66. PMID 10577520.
  • Buechler C, Ritter M, Orsó E, Langmann T, Klucken J, Schmitz G (January 2000). "Regulation of scavenger receptor CD163 expression in human monocytes and macrophages by pro- and antiinflammatory stimuli". Journal of Leukocyte Biology. 67 (1): 97–103. PMID 10648003.
  • Stover CM, Schleypen J, Grønlund J, Speicher MR, Schwaeble WJ, Holmskov U (2001). "Assignment of CD163B, the gene encoding M160, a novel scavenger receptor, to human chromosome 12p13.3 by in situ hybridization and somatic cell hybrid analysis". Cytogenetics and Cell Genetics. 90 (3–4): 246–7. doi:10.1159/000056781. PMID 11124526.
  • Kristiansen M, Graversen JH, Jacobsen C, Sonne O, Hoffman HJ, Law SK, Moestrup SK (January 2001). "Identification of the haemoglobin scavenger receptor". Nature. 409 (6817): 198–201. doi:10.1038/35051594. PMID 11196644.
  • Ritter M, Buechler C, Kapinsky M, Schmitz G (April 2001). "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. doi:10.1002/1521-4141(200104)31:4<999::AID-IMMU999>3.0.CO;2-R. PMID 11298324.
  • Sulahian TH, Hintz KA, Wardwell K, Guyre PM (June 2001). "Development of an ELISA to measure soluble CD163 in biological fluids". Journal of Immunological Methods. 252 (1–2): 25–31. doi:10.1016/S0022-1759(01)00328-3. PMID 11334962.
  • Högger P, Sorg C (November 2001). "Soluble CD163 inhibits phorbol ester-induced lymphocyte proliferation". Biochemical and Biophysical Research Communications. 288 (4): 841–3. doi:10.1006/bbrc.2001.5845. PMID 11688984.
  • Fonseca JE, Edwards JC, Blades S, Goulding NJ (May 2002). "Macrophage subpopulations in rheumatoid synovium: reduced CD163 expression in CD4+ T lymphocyte-rich microenvironments". Arthritis and Rheumatism. 46 (5): 1210–6. doi:10.1002/art.10207. PMID 12115225.
  • Frings W, Dreier J, Sorg C (August 2002). "Only the soluble form of the scavenger receptor CD163 acts inhibitory on phorbol ester-activated T-lymphocytes, whereas membrane-bound protein has no effect". FEBS Letters. 526 (1–3): 93–6. doi:10.1016/S0014-5793(02)03142-3. PMID 12208511.
  • Matsushita N, Kashiwagi M, Wait R, Nagayoshi R, Nakamura M, Matsuda T, Hogger P, Guyre PM, Nagase H, Matsuyama T (October 2002). "Elevated levels of soluble CD163 in sera and fluids from rheumatoid arthritis patients and inhibition of the shedding of CD163 by TIMP-3". Clinical and Experimental Immunology. 130 (1): 156–61. doi:10.1046/j.1365-2249.2002.01963.x. PMC 1906487. PMID 12296867.

External links