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Clinical Chemistry and Laboratory Medicine (CCLM)

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In This Section
Volume 52, Issue 3 (Mar 2014)


A soluble form of the macrophage-related mannose receptor (MR/CD206) is present in human serum and elevated in critical illness

Sidsel Rødgaard-Hansen
  • Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark
/ Aisha Rafique
  • Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark
/ Peter A. Christensen
  • Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark
/ Maciej B. Maniecki
  • Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark
/ Thomas D. Sandahl
  • Department of Medicine V, Aarhus University Hospital, Aarhus, Denmark
/ Ebba Nexø
  • Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark
/ Holger Jon Møller
  • Corresponding author
  • Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark
  • Email:
Published Online: 2013-10-11 | DOI: https://doi.org/10.1515/cclm-2013-0451


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.

This article offers supplementary material which is provided at the end of the article.

Keywords: biomarker; CD206; hepatitis; liver disease; M2 macrophage; sCD206; sepsis; sMR; soluble mannose receptor


  • 1.

    Martinez-Pomares L. The mannose receptor. J Leukoc Biol 2012;92:1177–86.

  • 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.

  • 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.

  • 4.

    Gordon S, Martinez FO. Alternative activation of macrophages: mechanism and functions. Immunity 2010;32:593–604. [Web of Science]

  • 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.

  • 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.

  • 7.

    Møller HJ. Soluble CD163. Scand J Clin Lab Invest 2012;72:1–13.

  • 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.

  • 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.

    Nordic Reference Interval Project. Aavailable from http://pweb.furst.no/norip/. Accessed on 21 December 2012.

  • 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.

  • 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.

  • 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. [Web of Science]

  • 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. [Web of Science]

  • 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. [Web of Science]

  • 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.

  • 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.

  • 18.

    Martinez FO, Sica A, Mantovani, Locati M. Macrophage activation and polarization. Front Biosci 2008;13:453–61. [PubMed] [Crossref] [Web of Science]

  • 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. [Web of Science]

  • 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. [PubMed] [Crossref] [Web of Science]

  • 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. [Crossref] [PubMed]

  • 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.

  • 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.

  • 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.

  • 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. [Web of Science]

  • 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. [Web of Science]

About the article

Corresponding author: Dr. Holger Jon Møller, Department of Clinical Biochemistry, Aarhus University Hospital, Nørrebrogade 44, 8000 Aarhus C, Denmark, Phone: +45 3120 2201, Fax: +45 7846 3060, E-mail:

Received: 2013-06-14

Accepted: 2013-09-04

Published Online: 2013-10-11

Published in Print: 2014-03-01

Citation Information: Clinical Chemistry and Laboratory Medicine, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2013-0451. Export Citation

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