A soluble form of the macrophage-related mannose receptor (MR/CD206) is present in human serum and elevated in critical illness
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Sidsel Rødgaard-Hansen
, Aisha Rafique , Peter A. Christensen , Maciej B. Maniecki , Thomas D. Sandahl , Ebba Nexø und Holger Jon Møller
Abstract
Background: This study tests the hypothesis that the mannose receptor (MR/CD206), which is expressed primarily by macrophages and dendritic cells, can be found in a soluble form (sMR, sMR) in human serum. Furthermore, we wished to establish and validate an enzyme-linked immunosorbent assay (ELISA) for sMR and to perform initial studies exploring the potential of sMR as a biomarker.
Methods: Western blotting identified a single band of approximately 170 kDa in human serum, and MALDI MS/MS of the purified protein confirmed it to be sMR. An ELISA was established and validated with a measurement range of 1–256 µg/L.
Results: The 95% reference interval was 0.10–0.43 mg/L based on measurements of serum samples from healthy individuals (n=217). Samples from hospitalised patients (n=219) revealed that more than 50% of patients had concentrations above 0.43 mg/L. Very high concentrations (up to 6.2 mg/L) were observed in critically ill patients with sepsis and/or severe liver disease.
Conclusions: This study documents, for the first time, the presence of sMR in human serum and describes an optimised ELISA suitable for quantitative measurements. Levels of sMR are strongly elevated in several disease states, including sepsis and liver disease, and the protein therefore shows promise as a new biomarker.
We thank laboratory technician Kirsten Bank Petersen for excellent technical assistance and The Danish Council for Strategic Research Funding (TRAIN 10-092797).
Conflict of interest statement
Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article.
Research funding: None declared.
Employment or leadership: Aarhus University holds patent applications for the use of sMR as a biomarker with Holger Jon Møller and Sidsel Rødgaard-Hansen as co-investigators.
Honorarium: None declared.
Authorship: SRH: Conception and design, collection of data, analysis and interpretation of data, critical revision of the manuscript, approval of the version to be published. AR: Collection of data, analysis and interpretation of data, critical revision of the manuscript, approval of the version to be published. PAC: Collection of data, analysis and interpretation of data, approval of the version to be published. MBM: Collection of data, analysis of data, approval of the version to be published. TS: Collection of data, analysis of data, approval of the version to be published. EN: Conception and design, interpretation of data, critical revision of the manuscript, approval of the version to be published. HJM: Conception and design, collection of data, analysis and interpretation of data, critical revision of the manuscript, approval of the version to be published, drafting the article.
References
1. Martinez-Pomares L. The mannose receptor. J Leukoc Biol 2012;92:1177–86.10.1189/jlb.0512231Suche in Google Scholar PubMed
2. Martínez-Pomares L, Mahoney JA, Káposzta R, Linehan SA, Stahl PD, Gordon S. A functional soluble form of the murine mannose receptor is produced by macrophages in vitro and is present in mouse serum. J Biol Chem 1998;273:23376–80.10.1074/jbc.273.36.23376Suche in Google Scholar PubMed
3. Jordens R, Thompson A, Amons R, Koning F. Human dendritic cells shed a functional, soluble form of the mannose receptor. Int Immunol 1999;11:1775–80.10.1093/intimm/11.11.1775Suche in Google Scholar PubMed
4. Gordon S, Martinez FO. Alternative activation of macrophages: mechanism and functions. Immunity 2010;32:593–604.10.1016/j.immuni.2010.05.007Suche in Google Scholar PubMed
5. Porcheray F, Viaud S, Rimaniol AC, Léone C, Samah B, Dereuddre-Bosquet N, et al. Macrophage activation switching: an asset for the resolution of inflammation. Clin Exp Immunol 2005;142:481–9.10.1111/j.1365-2249.2005.02934.xSuche in Google Scholar PubMed PubMed Central
6. Møller HJ, Peterslund NA, Graversen JH, Moestrup SK. Identification of the hemoglobin scavenger receptor/CD163 as a natural soluble protein in plasma. Blood 2002;99:378–80.10.1182/blood.V99.1.378Suche in Google Scholar
7. Møller HJ. Soluble CD163. Scand J Clin Lab Invest 2012;72:1–13.10.3109/00365513.2011.626868Suche in Google Scholar PubMed
8. Møller HJ, Frikke-Schmidt R, Moestrup SK, Nordestgaard BG, Tybjærg-Hansen A. Serum soluble CD163 predicts risk of type 2 diabetes in the general population. Clin Chem 2011;57:291–7.10.1373/clinchem.2010.154724Suche in Google Scholar PubMed
9. Grønbæk H, Sandahl TD, Mortensen TD, Vilstrup H, Møller HJ, Møller S. Soluble CD163, a marker of Kupffer cell activation, is related to portal hypertension in patients with liver cirrhosis. Aliment Pharmacol Ther 2012;36:173–80.10.1111/j.1365-2036.2012.05134.xSuche in Google Scholar PubMed
10. Nordic Reference Interval Project. Aavailable from http://pweb.furst.no/norip/. Accessed on 21 December 2012.Suche in Google Scholar
11. Møller HJ, Hald K, Moestrup SK. Characterization of an enzyme-linked immunosorbent assay for soluble CD163. Scand J Clin Lab Invest 2002;62:293–9.10.1080/003655102760145852Suche in Google Scholar PubMed
12. Danish Institute for External Quality Assurance for Laboratories in Health Care, DEKS. Available from http://www.deks.dk/index.html. Accessed on 21 December 2012.Suche in Google Scholar
13. Parkner T, Sørensen LP, Nielsen AR, Fischer CP, Bibby BM, Nielsen S, et al. Soluble CD163: a biomarker linking macrophages and insulin resistance. Diabetologia 2012;55:1856–62.10.1007/s00125-012-2533-1Suche in Google Scholar
14. Holland-Fischer P, Grønbæk H, Sandahl TD, Moestrup SK, Riggio O, Ridola L, et al. Kupffer cells are activated in cirrhotic portal hypertension and not normalised by TIPS. Gut 2011;60:1389–93.10.1136/gut.2010.234542Suche in Google Scholar
15. Feng L, Zhou X, Su LX, Feng D, Jia YH, Xie LX. Clinical significance of soluble hemoglobin scavenger receptor CD163 (sCD163) in sepsis, a prospective study. PLoS One 2012;7:e38400.10.1371/journal.pone.0038400Suche in Google Scholar
16. Møller HJ, Moestrup SK, Weis N, Wejse C, Nielsen H, Pedersen SS, et al. Macrophage serum markers in pneumococcal bacteremia: prediction of survival by soluble CD163. Crit Care Med 2006;34:2561–6.10.1097/01.CCM.0000239120.32490.ABSuche in Google Scholar
17. Subramanian S, Tawakol A, Burdo TH, Abbara S, Wei J, Vijayakumar J, et al. Arterial inflammation in patients with HIV. J Am Med Assoc 2012;308:379–86.10.1001/jama.2012.6698Suche in Google Scholar
18. Martinez FO, Sica A, Mantovani, Locati M. Macrophage activation and polarization. Front Biosci 2008;13:453–61.10.2741/2692Suche in Google Scholar
19. Etzerodt A, Maniecki MB, Møller K, Møller HJ, Moestrup SK. Tumor necrosis factor α-converting enzyme (TACE/ADAM17) mediates ectodomain shedding of the scavenger receptor CD163. J Leukoc Biol 2010;88:1201–5.10.1189/jlb.0410235Suche in Google Scholar
20. Kneidl J, Löffler B, Kalinka J, Peters G, Roth J, Barczyk K. Soluble CD163 promotes recognition, phagocytosis and killing of Staphylococcus aureus via binding of specific fibronectin peptides. Cell Microbiol 2012;14:914–36.10.1111/j.1462-5822.2012.01766.xSuche in Google Scholar
21. Fraser IP, Takahashi K, Koziel H, Fardin B, Harmsen A, Ezekowitz RA. Pneumocystis carinii enhances soluble mannose receptor production by macrophages. Microbes Infect 2000;2:1305–10.10.1016/S1286-4579(00)01283-1Suche in Google Scholar
22. Gazi U, Rosas M, Singh S, Heinsbroek S, Haq I, Johnson S, et al. Fungal recognition enhances mannose receptor shedding through dectin-1 engagement. J Biol Chem 2011;286:7822–9.10.1074/jbc.M110.185025Suche in Google Scholar PubMed PubMed Central
23. Su Y, Bakker T, Harris J, Tsang C, Brown GD, Wormald MR, et al. Glycosylation influences the lectin activities of the macrophage mannose receptor. J Biol Chem 2005;280: 32811–20.10.1074/jbc.M503457200Suche in Google Scholar PubMed
24. Zamze S, Martinez-Pomares L, Jones H, Taylor PR, Stillion RJ, Gordon S, et al. Recognition of bacterial capsular polysaccharides and lipopolysaccharides by the macrophage mannose receptor. J Biol Chem 2002;277:41613–23.10.1074/jbc.M207057200Suche in Google Scholar PubMed
25. Møller HJ, Nielsen MJ, Maniecki MB, Madsen M, Moestrup SK. Soluble macrophage-derived CD163: a homogenous ectodomain protein with a dissociable haptoglobin-hemoglobin binding. Immunobiology 2010;215:406–12.10.1016/j.imbio.2009.05.003Suche in Google Scholar PubMed
26. Palmieri C, Caley MP, Purshouse K, Fonseca AV, Rodriguez-Teja M, Kogianni G, et al. Endo180 modulation by bisphosphonates and diagnostic accuracy in metastatic breast cancer. Br J Cancer 2013;108:163–9.10.1038/bjc.2012.540Suche in Google Scholar PubMed PubMed Central
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- Editorial
- Point of care testing: evolving scenarios and innovative perspectives
- Review
- Point-of-care testing: where is the evidence? A systematic survey
- Mini Review
- Vulnerability of point-of-care test reagents and instruments to environmental stresses: implications for health professionals and developers
- Opinion Paper
- Twenty-five years of idiopathic calcium nephrolithiasis: has anything changed?
- Genetics and Molecular Diagnostics
- Optimizing the purification and analysis of miRNAs from urinary exosomes
- General Clinical Chemistry and Laboratory Medicine
- Extensive study of human insulin immunoassays: promises and pitfalls for insulin analogue detection and quantification
- Absorptive chemistry based extraction for LC-MS/MS analysis of small molecule analytes from biological fluids – an application for 25-hydroxyvitamin D
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