Skip to main content
Log in

YKL-40 protein expression in normal adult human tissues – an immunohistochemical study

  • Original Paper
  • Published:
Journal of Molecular Histology Aims and scope Submit manuscript

An Erratum to this article was published on 10 July 2007

Abstract

YKL-40, a 40 kDa plasma protein, is secreted by macrophages, neutrophils, chondrocytes, vascular smooth muscle cells and cancer cells. High plasma YKL-40 is found in patients with inflammatory diseases and cancer, but it is not known how the protein is expressed in tissues. This immunohistochemical study was carried out with the purpose of mapping and grading cytoplasmic expression of YKL-40 in normal human tissue. Bovine serum albumin had to be used for pre-incubation in order to eliminate background staining of YKL-40. The majority of cells were stained, but the intensity varied, not just among different cell types but also within the same cell type. Cells known for exerting a high metabolic activity, i.e., high producing cells or cells with high turn-over, tended to show the most intense cytoplasmic staining, which was weak or lacking in cells with no or little activity. Many of these positive cells probably contribute to the YKL-40 found in plasma in healthy subjects in accordance with previous findings on their in vitro production of the protein. In conclusion, all cells with a functioning nucleus appeared to be capable of expressing YKL-40 in their cytoplasm, the intensity of which was dependent on cellular activity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Baeten D, Boots AM, Steenbakkers PG, Elewaut D, Bos E, Verheijden GF, Berheijden G et al (2000) Human cartilage gp-39+, CD16+ monocytes in peripheral blood and synovium: correlation with joint destruction in rheumatoid arthritis. Arthritis Rheum 43:1233–1243

    Article  PubMed  CAS  Google Scholar 

  • Bernardi D, Podswiadek M, Zaninotto M, Punzi L, Plebani M (2003) YKL-40 is a marker of joint involvement in inflammatory bowel disease. Clin Chem 49:1685–1688

    Article  PubMed  CAS  Google Scholar 

  • Boot RG, van Achterberg TA, van Aken BE, Renkema GH, Jacobs MJ, Aerts JM, de Vries CJ (1999) Strong induction of members of the chitinase family of proteins in atherosclerosis: chitotriosidase and human cartilage gp-39 expressed in lesion macrophages. Arterioscler Thromb Vasc Biol 19:687–694

    PubMed  CAS  Google Scholar 

  • Dasuri K, Antonovici M, Chen K, Wong K, Standing K, Ens W, El-Gabalawy H et al (2004) The synovial proteome: analysis of fibroblast-like synoviocytes. Arthritis Res Ther 6:R161–R168

    Article  PubMed  CAS  Google Scholar 

  • De Ceuninck F, Gaufillier S, Bonnaud A, Sabatini M, Lesur C, Pastoureau P (2001) YKL-40 (cartilage gp-39) induces proliferative events in cultured chondrocytes and synoviocytes and increases glycosaminoglycan synthesis in chondrocytes. Biochem Biophys Res Commun 285:926–931

    Article  PubMed  CAS  Google Scholar 

  • Fukushima N, Koopmann J, Sato N, Prasad N, Carvalho R, Leach SD, Hruban RH et al (2005) Gene expression alterations in the non-neoplastic parenchyma adjacent to infiltrating pancreatic ductal adenocarcinoma. Modern Pathol 18:779–787

    Article  CAS  Google Scholar 

  • Fusetti F, Pijning T, Kalk KH, Bos E, Dijkstra BW (2003) Crystal structure and carbohydrate binding properties of the human cartilage glycoprotein-39. J Biol Chem 278:37753–37760

    Article  PubMed  CAS  Google Scholar 

  • Hakala BE, White C, Recklies AD (1993) Human cartilage gp-39, a major secretory product of articular chondrocytes and synovial cells, is a mammalian member of a chitinase protein family. J Biol Chem 268:25803–25810

    PubMed  CAS  Google Scholar 

  • Hashimoto S, Suzuki T, Dong HY, Yamazaki N, Matsushima K (1999) Serial analysis of gene expression in human monocytes and macrophages. Blood 94:837–844

    PubMed  CAS  Google Scholar 

  • Harvey S, Weisman M, O’Dell J, Scott T, Krusemeier M, Visor J, Swindlehurst C (1998) Chondrex: new marker of joint disease. Clin Chem 44:509–516

    PubMed  CAS  Google Scholar 

  • Houston DR, Recklies AD, Krupa JC, van Aalten DMF (2003) Structure and ligand induced conformational change of the 39-kDa glycoprotein from human articular chondrocytes. J Biol Chem 278:30206–30212

    Article  PubMed  CAS  Google Scholar 

  • Huang Y, Prasad M, Lemon WJ, Hampel H, Wright FA, Kornacker K, LiVolsi V et al (2001) Gene expression in papillary thyroid carcinoma reveals highly consistent profiles. Proc Natl Acad Sci USA 98:15044–15049

    Article  PubMed  CAS  Google Scholar 

  • Johansen JS, Williamson MK, Rice JS, Price PA (1992) Identification of proteins secreted by human osteoblastic cells in culture. J Bone Miner Res 7:501–512

    Article  PubMed  CAS  Google Scholar 

  • Johansen JS, Hvolris J, Hansen M, Backer V, Lorenzen I, Price PA (1996) Serum YKL-40 levels in healthy children and adults. Comparison with serum and synovial fluid levels of YKL-40 in patients with osteoarthritis or trauma of the knee joint. Br J Rheumatol 35:553–559

    Article  PubMed  CAS  Google Scholar 

  • Johansen JS, Baslund B, Garbarsch C, Hansen M, Stoltenberg M, Lorenzen I, Price PA (1999) YKL-40 in giant cells and macrophages from patients with giant cell arteritis. Arthritis Rheum 42:2624–2630

    Article  PubMed  CAS  Google Scholar 

  • Johansen JS, Christoffersen P, Møller S, Price PA, Henriksen JH, Garbarsch C, Bendtsen F (2000) Serum YKL-40 is increased in patients with hepatic fibrosis. J Hepatol 32:911–920

    Article  PubMed  CAS  Google Scholar 

  • Johansen JS, Olee T, Price PA, Hashimoto S, Ochs RL, Lotz M (2001) Regulation of YKL-40 production by human articular chondrocytes. Arthritis Rheum 44:826–837

    Article  PubMed  CAS  Google Scholar 

  • Johansen JS, Milman N, Hansen M, Garbarsch C, Price PA, Graudal N (2005) Increased serum YKL-40 in patients with pulmonary sarcoidosis. A potential marker of disease activity? Resp Med 99:396–402

    Article  Google Scholar 

  • Johansen JS, Jensen BV, Roslind A, Nielsen D, Price PA (2006) Review. Serum YKL-40, a new prognostic biomarker in cancer patients? Cancer Epidemiol Biomarkers Prev 15:194–202

    Article  PubMed  CAS  Google Scholar 

  • Junker N, Johansen JS, Andersen CB, Kristjansen PEG (2005a) Expression of YKL-40 by peritumoral macrophages in human small cell lung cancer. Lung Cancer 48:223–231

    Article  Google Scholar 

  • Junker N, Johansen JS, Hansen LT, Lund EL, Kristjansen PEG (2005b) Regulation of YKL-40 expression during genotoxic or microenvironmental stress in human glioblastoma cells. Cancer Sci 96:183–190

    Article  CAS  Google Scholar 

  • Kamal SM, Turner B, He Q, Rasenack J, Bianchi L, Al Tawil A, Nooman A et al (2006) Progression of fibrosis in hepatitis C with and without schistosomiasis: correlation with serum markers of fibrosis. Hepatology 43:771–779

    Article  PubMed  CAS  Google Scholar 

  • Kawasaki M, Hasegawa Y, Kondo S, Iwata H (2001) Concentration and localization of YKL-40 in hip joint diseases. J Rheumatol 28:341–345

    PubMed  CAS  Google Scholar 

  • Kirkpatrick RB, Emery JG, Connor JR, Dodds R, Lysko PG, Rosenberg M (1997) Induction and expression of human cartilage glycoprotein 39 in rheumatoid inflammatory and peripheral blood monocyte-derived macrophages. Exp Cell Res 237:46–54

    Article  PubMed  CAS  Google Scholar 

  • Koutroubakis IE, Petinaki E, Dimoulios P, Vardas E, Roussomoustakaki M, Maniatis AN, Kouroumalis EA (2003) Increased serum levels of YKL-40 in patients with inflammatory bowel disease. Int J Colorectal Dis 18:254–259

    PubMed  Google Scholar 

  • Kronborg G, Østergaard C, Weis N, Nielsen H, Obel N, Pedersen SS, Price PA et al (2002) Serum level of YKL-40 is elevated in patients with Streptococcus pneumoniae bacteremia and is associated to the outcome of the disease. Scand J Infect Dis 34:323–326

    Article  PubMed  Google Scholar 

  • Lal A, Lash AE, Altschul SF, Velculescu V, Zhang L, McLendon RE, Marra MA et al (1999) A public database for gene expression in human cancers. Cancer Res 59:5403–5407

    PubMed  CAS  Google Scholar 

  • Ling H, Recklies AD (2004) The chitinase 3-like protein human cartilage glycoprotein 39 inhibits cellular response to the inflammatory cytokines interleukin-1 and tumour necrosis factor-α. Biochem J 380:651–659

    Article  PubMed  CAS  Google Scholar 

  • Malinda KM, Ponce L, Kleinman HK, Shackelton LM, Millis AJ (1999) Gp38k, a protein synthesized by vascular smooth muscle cells, stimulates directional migration of human umbilical vein endothelial cells. Exp Cell Res 250:168–173

    Article  PubMed  CAS  Google Scholar 

  • Markert JM, Fuller CM, Gillespie GY, Bubien JK, McLean LA, Hong RL, Lee K et al (2001) Differential gene expression profiling in human brain tumors. Physiol Genomics 5:21–33

    PubMed  CAS  Google Scholar 

  • Matsumoto T, Tsuromoto T (2001) Serum YKL-40 levels in rheumatoid arthritis: correlations between clinical and laboratory parameters. Clin Exp Rheumatol 19:655–660

    PubMed  CAS  Google Scholar 

  • Morrison BW, Leder P (1994) neu and ras initiate murine mammary tumors that share genetic markers generally absent in c-myc and int-2-initiated tumors. Oncogene 9:3417–3426

    PubMed  CAS  Google Scholar 

  • Nigro JM, Misra A, Zhang L, Smirnov I, Colman H, Griffin C, Ozburn N et al (2005) Integrated array-comparative genomic hybridization and expression array profiles identify clinically relevant molecular subtypes of glioblastoma. Cancer Res 65:1678–1686

    Article  PubMed  CAS  Google Scholar 

  • Nishikawa KC, Millis AJT (2003) gp38k (CHI3L1) is a novel adhesion and migration factor for vascular cells. Exp Cell Res 287:79–87

    Article  PubMed  CAS  Google Scholar 

  • Nordenbaek C, Johansen JS, Junker P, Borregaard N, Sorensen O, Price PA (1999) YKL-40, a matrix protein of specific granules in neutrophils, is elevated in serum of patients with community-acquired pneumonia requiring hospitalization. J Infect Dis 180:1722–1726

    Article  PubMed  CAS  Google Scholar 

  • Nutt CL, Betensky RA, Brower MA, Batchelor TT, Louis DN, Stemmer-Rachamimow AO (2005) YKL-40 is a different diagnostic marker for histologic subtypes of high-grade gliomas. Clin Cancer Res 11:2258–2264

    Article  PubMed  CAS  Google Scholar 

  • Nyirkos P, Golds EE (1990) Human synovial cells secrete a 39 kDa protein similar to a bovine mammary protein expressed during the non-lactating period. Biochem J 268:265–268

    Google Scholar 

  • Nøjgaard C, Johansen JS, Christensen E, Skovgaard LT, Price PA, Becker U, the EMALD Group (2003) Serum levels of YKL-40 and PIIINP as prognostic markers in patients with alcoholic liver disease. J Hepatol 39:179–186

    Google Scholar 

  • Pelloski CE, Mahajan A, Maor M, Chang EL, Woo S, Gilbert M, Colman H et al (2005) YKL-40 expression is associated with poorer response to radiation and shorter overall survival in glioblastoma. Clin Cancer Res 11:3326–3334

    Article  PubMed  CAS  Google Scholar 

  • Peltomaa R, Paimela L, Harvey S, Helve T, Leirisalo-Repo M (2001) Increased level of YKL-40 in sera from patients with early rheumatoid arthritis: a new marker for disease activity. Rheumatol Int 20:192–196

    Article  PubMed  CAS  Google Scholar 

  • Recklies AD, White C, Ling H (2002) The chitinase 3-like protein human cartilage glycoprotein 39 (HC-gp39) stimulates proliferation of human connective-tissue cells and activates both extracellular signal-regulated kinase- and protein kinase B-mediated signalling pathways. Biochem J 365:119–126

    Article  PubMed  CAS  Google Scholar 

  • Rehli M, Krause SW, Andresen R (1997) Molecular characterization of the gene for human cartilage gp-39 (CHI3L1), a member of the chitinase protein family and marker for late stages of macrophage differentiation. Genomics 43:221–225

    Article  PubMed  CAS  Google Scholar 

  • Rehli M, Niller HH, Ammon C, Langemann S, Schwarzfischer L, Andreesen R, Krause SW (2003) Transcriptional regulation of (CHI3L1), a marker gene for late stages of macrophage differentiation. J Biol Chem 278:44058–44067

    Article  PubMed  CAS  Google Scholar 

  • Renkema GH, Boot RG, Au FL, Donker-Koopman WE, Strijland A, Muijsers AO, Hrebicek M et al (1998) Chitotriosidase, a chitinase, and the 39-kDa human cartilage glycoprotein, a chitin-binding lectin, are homologues of family 18 glycosyl hydrolases secreted by human macrophages. Eur J Biochem 251:504–509

    Article  PubMed  CAS  Google Scholar 

  • Shackelton LM, Mann DM, Millis AJT (1995) Identification of a 38-kDa heparin-binding glycoprotein (gp38k) in differentiating vascular smooth muscle cells as a member of a group of proteins associated with tissue remodelling. J Biol Chem 270:13076–13083

    Article  PubMed  CAS  Google Scholar 

  • Sjögren H, Meis-Kindblom JM, Ôrndal C, Bergh P, Ptaszynski K, Åman P, Kindblom LG et al (2003) Studies on the molecular pathogenesis of extraskeletal myxoid chondrosarcoma-cytogenetic, molecular genetic, and cDNA microarray analyses. Am J Pathol 162:781–792

    PubMed  Google Scholar 

  • Suzuki T, Hashimoto S, Toyoda N, Nagai S, Yamazaki N, Dong H-Y, Sakai J et al (2000) Comprehensive gene expression profile of LPS-stimulated human monocytes by SAGE. Blood 96:2584–2591

    PubMed  CAS  Google Scholar 

  • Tanwar MK, Gilbert MR, Holland EC (2002) Gene expression microarray analysis reveals YKL-40 to be a potential serum marker for malignant character in human glioma. Cancer Res 62:4364–4368

    PubMed  CAS  Google Scholar 

  • Tran A, Benzaken S, Saint-Paul MC, Guzman-Granier E, Hastier P, Pradier C, Barjoan EM et al (2000) Chondrex (YKL-40), a potential new serum fibrosis marker in patients with alcoholic liver disease. Eur J Gastroenterol Hepatol 12:989–993

    Article  PubMed  CAS  Google Scholar 

  • Verhoeckx KCM, Bijlsma S, de Groene EM, Witkamp RF, van der Greef J, Rodenburg RJT (2004) A comparison of proteomics, principal component analysis and transcriptomics is a powerful tool for the identification of biomarkers for macrophage maturation in the U937 cell line. Proteomics 4:1014–1028

    Article  PubMed  CAS  Google Scholar 

  • Vind I, Johansen JS, Price PA, Munkholm P (2003) Serum YKL-40, a potential new marker of disease activity in patients with inflammatory bowel disease. Scand J Gastroenterol 38:599–605

    Article  PubMed  CAS  Google Scholar 

  • Volck B, Price PA, Johansen JS, Sørensen O, Benfield TL, Nielsen HJ, Calafat J et al (1998) YKL-40, a mammalian member of the chitinase family, is a matrix protein of specific granules in human neutrophils. Proc Assoc Am Physicians 4:351–360

    Google Scholar 

  • Volck B, Østergaard K, Johansen JS, Garbarsch C, Price PA (1999) The distribution of YKL-40 in osteoartrhitic and normal human articular cartilage. Scand J Reumatol 28:171–179

    Article  CAS  Google Scholar 

  • Volck B, Johansen JS, Stoltenberg M, Garbarsch C, Price PA, Østergaard M, Ostergaard K et al (2001) Studies on YKL-40 in knee joints of patients with rheumatoid arthritis and osteoarthritis. Involvement of YKL-40 in the joint pathology. Osteoarthritis Cartilage 9:203–214

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We want to thank technologist Hanife Dzaferi, Drs. Anne Roslind and Eva Balslev, Herlev Hospital, University of Copenhagen and technologist Heidi Marie Paulsen, Rigshospitalet, University of Copenhagen, for technical support. We also want to thank Drs. Helle Broholm and Søren Daugaard, Rigshospitalet, University of Copenhagen, and Dr. Bente Pakkenberg, Bispebjerg Hospital, University of Copenhagen for supply of tissue sections from brain, cartilage and bone.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Merete Ringsholt.

Additional information

An erratum to this article can be found at http://dx.doi.org/10.1007/s10735-007-9100-y

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ringsholt, M., Høgdall, E.V.S., Johansen, J.S. et al. YKL-40 protein expression in normal adult human tissues – an immunohistochemical study. J Mol Hist 38, 33–43 (2007). https://doi.org/10.1007/s10735-006-9075-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10735-006-9075-0

Keywords

Navigation