Inflammation Research

, Volume 58, Issue 8, pp 503–512 | Cite as

Detection of galectin-3 in patients with inflammatory bowel diseases: new serum marker of active forms of IBD?

  • Lenka Frol’ová
  • Karel SmetanaJr
  • Dana Borovská
  • Andrea Kitanovičová
  • Klára Klimešová
  • Ivana Janatková
  • Karin Malíčková
  • Milan Lukáš
  • Pavel Drastich
  • Zdeněk Beneš
  • Ludmila Tučková
  • Joachim C. Manning
  • Sabine André
  • Hans-Joachim Gabius
  • Helena Tlaskalová-Hogenová
Original Research Paper

Abstract

Objective

It is an open question whether multifunctional galectin-3 can be a serum marker in inflammatory bowel disease.

Methods

Western blots and commercial ELISA detected and quantitated the lectin immunocytochemistry using double labeling localized it in tissue sections.

Results

Serum concentrations were significantly increased in specimen of patients with active and remission-stage ulcerative colitis and Crohn’s disease, associated with emerging positivity of CD14+ cells.

Conclusion

Enhanced concentration of galectin-3 in serum reflects presence of disease and points to its involvement in the pathogenesis.

Keywords

Crohn’s disease Galectin-3 Disease marker Mucosal immunity Ulcerative colitis 

References

  1. 1.
    Gabius H-J. Cell surface glycans: the why and how of their functionality as biochemical signals in lectin-mediated information transfer. Crit Rev Immunol. 2006;26:43–79.PubMedGoogle Scholar
  2. 2.
    Villalobo A, Nogales-González A, Gabius H-J. A guide to signaling pathways connecting protein-glycan interaction with the emerging versatile effector functionality of mammalian lectins. Trends Glycosci Glycotechnol. 2006;18:1–37.Google Scholar
  3. 3.
    Dimic J, Dabelic S, Flögel M. Galectin-3: and open-ended story. Biochim Biophys Acta. 2006;1760:616–35.Google Scholar
  4. 4.
    Gabius HJ. Animal lectins. Eur J Biochem. 1997;243:543–76.PubMedCrossRefGoogle Scholar
  5. 5.
    Ahmad N, Gabius H-J, André S, Kaltner H, Sabesan S, Roy R, et al. Galectin-3 precipitates as a pentamer with synthetic carbohydrates and forms heterogeneous cross-linked complexes. J Biol Chem. 2004;279:10841–7.PubMedCrossRefGoogle Scholar
  6. 6.
    Almkvist J, Karlsson A. Galectins as inflammatory mediators. Glycoconj J. 2004;19:575–81.PubMedCrossRefGoogle Scholar
  7. 7.
    Kübler D, Hung C-W, Dam TK, Kopitz J, André S, Kaltner H, et al. Phosphorylated human galectin-3: facile large-scale preparation of active lectin and detection of structural changes by CD spectroscopy. Biochim Biophys Acta. 2008;1780:716–22.PubMedGoogle Scholar
  8. 8.
    Shanahan F. Inflammatory bowel disease: immunodiagnostics, immunotherapeutics, and ecotherapeutics. Gastroenterology. 2001;120:622–35.PubMedCrossRefGoogle Scholar
  9. 9.
    Hibi T, Ogata H. Novel pathophysiological concepts of inflammatory bowel disease. J Gastroenterol. 2006;41:10–6.PubMedCrossRefGoogle Scholar
  10. 10.
    Scaldaferri F, Fiocchi C. Inflammatory bowel disease: progress and current concepts of etiopathogenesis. J Dig Dis. 2007;8:171–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Iurisci I, Tinari N, Natoli C, Angelucci D, Cianchetti E, Iacobelli S. Concentrations of galectin-3 in the sera of normal controls and cancer patients. Clin Cancer Res. 2000;6:1389–93.PubMedGoogle Scholar
  12. 12.
    Jensen-Jarolin E, Neumann C, Oberhuber G, Gscheidlinger R, Neuchrist C, Reinisch W, et al. Anti-galectin-3 IgG autoantobodies in patients with Crohn’s disease characterized by means of phage display peptide libraries. J Clin Immunol. 2001;21:348–56.CrossRefGoogle Scholar
  13. 13.
    Best WR. Predicting the Crohn’s disease activity index from the Harvey-Bradshaw Index. Inflamm Bowel Dis. 2006;12:304–10.PubMedCrossRefGoogle Scholar
  14. 14.
    Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005;353:2462–76.PubMedCrossRefGoogle Scholar
  15. 15.
    Schroeder KW, Tremaine WJ, Ilstrup DM (1987) Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N Engl J Med 24;317:1625-9.Google Scholar
  16. 16.
    Kopitz J, von Reitzenstein C, André S, Kaltner H, Uhl J, Ehemann V, et al. Negative regulation of neuroblastoma cell growth by carbohydrate- dependent surface binding of galectin-1 and functional divergence from galectin-3. J Biol Chem. 2001;276:35917–23.PubMedCrossRefGoogle Scholar
  17. 17.
    Beer A, André S, Kaltner H, Lensch M, Franz S, Sarter K, et al. Human galectins as sensors for apoptosis/necrosis-associated surface changes of granulocytes and lymphocytes. Cytom Part A. 2008;73A:139–47.CrossRefGoogle Scholar
  18. 18.
    Hudcovic T, Stepankova R, Cebra J, Tlaskalova-Hogenova H. The role of microflora in the development of intestinal inflammation: acute and chronic colitis induced by dextran sulfate in germ-free and conventionally reared immunocompetent and immunodeficient mice. Folia Microbiol (Praha). 2001;46:565–72.CrossRefGoogle Scholar
  19. 19.
    Cooper HS, Murthy SN, Shah RS, Sedergran DJ. Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest. 1993;69:238–49.PubMedGoogle Scholar
  20. 20.
    Lodinova-Zadnikova R, Cukrowska B, Tlaskalova-Hogenova H. Oral administration of probiotic Escherichia coli after birth reduces frequency of allergies and repeated infections later in life (after 10 and 20 years). Int Arch Allergy Immunol. 2003;131:209–11.PubMedCrossRefGoogle Scholar
  21. 21.
    Kwapinski JBG. Methodology of Immunochemical and Immunological Research. New York: Wiley; 1972. p. 605–7.Google Scholar
  22. 22.
    André S, Kojima S, Yamazaki N, Fink C, Kaltner H, Kayser K, et al. Galectins-1 and -3 and their ligands in tumor biology. J Cancer Res Clin Oncol. 1999;125:461–74.PubMedCrossRefGoogle Scholar
  23. 23.
    Froňková V, Holíková Z, Liu F-T, Homolka J, Rijken DC, André S, et al. Simultaneous detection of endogenous lectins and their binding capability at the single-cell level: a technical note. Folia Biol (Praha). 1999;45:157–62.Google Scholar
  24. 24.
    Dam TK, Gabius H-J, André S, Kaltner H, Lensch M, Brewer CF. Galectins bind to the multivalent glycoprotein asialofetuin with enhanced affinities and a gradient of decreasing binding constants. Biochemistry. 2005;44:12564–71.PubMedCrossRefGoogle Scholar
  25. 25.
    Gabius HJ, Schröter C, Gabius S, Brinck U, Tietze LF. Binding of T-antigen-bearing neoglycoprotein and peanut agglutinin to cultured tumor cells and breast carcinomas. J Histchem Cytochem. 1990;38:1625–31.Google Scholar
  26. 26.
    Gabius HJ, Gabius S, Zemlyanukhina TV, Bovin NV, Brinck U, Danguy A, et al. Reverse lectin histochemistry: design and application of glycoligands for detection of cell and tissue lectins. Histol Histopathol. 1993;8:369–83.PubMedGoogle Scholar
  27. 27.
    Plzák J, Betka J, Smetana K Jr, Chovanec M, Kaltner H, André S, et al. Galectin-3: an emerging prognostic indicator in advanced head and neck carcinoma. Eur J Cancer. 2004;40:2324–30.PubMedCrossRefGoogle Scholar
  28. 28.
    Gabius HJ, Wosgien B, Hendrys M, Bardosi A. Lectin localization in human nerve by biochemically defined lectin-binding glycoproteins, neogycoprotein and lectin-specific antibody. Histochemistry. 1991;95:269–77.PubMedCrossRefGoogle Scholar
  29. 29.
    Lohr M, Lensch M, André S, Kaltner H, Siebert HC, Smetana K Jr, et al. Murine homodimeric adhesion/growth-regulatory galectins-1, -2, and -7: comparative profiling of gene/promoter sequences by database mining, of expression by RT-PCR/immunohistochemsitry and of contact sites for carbohydrate ligands by computational chemistry. Folia Biol (Praha). 2007;53:109–28.Google Scholar
  30. 30.
    Jensen-Jarolim E, Gscheidlinger R, Oberhuber G, Neuchrist C, Lucas T, Bises G, et al. The constitutive expression of galectin-3 is downregulated in the intestinal epithelia of Crohn’s disease patients, and tumour necrosis factor-α decreases the level of galectin-3-specific mRNA in HCT-8 cells. Eur J Gastroenterol Hepatol. 2002;14:145–52.PubMedCrossRefGoogle Scholar
  31. 31.
    Müller S, Schaffer T, Flogerzi B, Fleetwood A, Weimann R, Schoepfer AM, et al. Galectin-3 modulates T cell activity and is reduced in the inflamed intestinal epithelium in IBD. Inflamm Bowel Dis. 2006;12:588–97.PubMedCrossRefGoogle Scholar
  32. 32.
    Shiobara N, Suzuki Y, Aoki H, Gotoh A, Fujii Y, Hamada Y, et al. Bacterial superantigens and T cell receptor β-chain-bearing T cells in the immunopathogenesis of ulcerative colitis. Clin Exp Immunol. 2007;150:13–21.PubMedGoogle Scholar
  33. 33.
    Saussez S, Glinoer D, Chantrain G, Pattou F, Carnaille B, André S, et al. Serum galectin-1 and galectin-3 levels in benign and malignant nodular thyroid disease. Thyroid. 2008;18:705–12.PubMedCrossRefGoogle Scholar
  34. 34.
    Okayasu I, Hatakeyama S, Yamada M, Ohkusa T, Inagaki Y, Nakaya R. A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology. 1990;98:694–702.PubMedGoogle Scholar
  35. 35.
    Hamdani G, Gabet Y, Rachmilewitz D, Karmeli F, Bab I, Dresner-Pollak R. Dextran sodium sulfate-induced colitis causes rapid bone loss in mice. Bone. 2008;43:945–50.PubMedCrossRefGoogle Scholar
  36. 36.
    Subramanian S, Roberts CL, Hart CA, Martin HM, Edwards SW, Rhodes JM, et al. Replication of colonic crohn’s disease mucosal Escherichia coli isolates within macrophages and their susceptibility to antibiotics. Antimicrob Agents Chemother. 2008;52:427–34.PubMedCrossRefGoogle Scholar
  37. 37.
    Tlaskalova-Hogenova H, Stepankova R, Hudcovic T, Tuckova L, Cukrowska B, Lodinova-Zadnikova R, et al. Commensal bacteria (normal microflora), mucosal immunity and chronic inflammatory and autoimmune diseases. Immunol Lett. 2004;93:97–108.PubMedCrossRefGoogle Scholar
  38. 38.
    Elson CO, Cong Y, McCracken VJ, Dimmitt RA, Lorenz RG, Weaver CT. Experimental models of inflammatory bowel disease reveal innate, adaptive, and regulatory mechanisms of host dialogue with the microbiota. Immunol Rev. 2005;206:260–76.PubMedCrossRefGoogle Scholar
  39. 39.
    Swidsinski A, Weber J, Loening-Baucke V, Hale LP, Lochs H. Spatial organization and composition of the mucosal flora in patients with inflammatory bowel disease. J Clin Microbiol. 2005;43:3380–9.PubMedCrossRefGoogle Scholar
  40. 40.
    Sydora BC, Martin SM, Lupicki M, Dieleman LA, Doyle J, Walker JW, et al. Bacterial antigens alone can influence intestinal barrier integrity, but live bacteria are required for initiation of intestinal inflammation and injury. Inflamm Bowel Dis. 2006;12:429–36.PubMedCrossRefGoogle Scholar
  41. 41.
    Stepankova R, Powrie F, Kofronova O, Kozakova H, Hudcovic T, Hrncir T, et al. Segmented filamentous bacteria in a defined bacterial cocktail induce intestinal inflammation in SCID mice reconstituted with CD45RBhigh CD4 + T cells. Inflamm Bowel Dis. 2007;13:1202–11.PubMedCrossRefGoogle Scholar
  42. 42.
    Ogra PL, Mestecky J, Lamm ME, Strober W, Bienenstock J, McGhee JR. Mucosal Immunology. New York: Academic; 1999.Google Scholar
  43. 43.
    Walker WAJ. Development of the intestinal mucosal barrier. Pediatr Gastroenterol Nutr. 2002;34:S33–9.CrossRefGoogle Scholar
  44. 44.
    Tlaskalová-Hogenová H, Tucková L, Stepánková R, Hudcovic T, Palová-Jelínková L, Kozáková H, et al. Involvement of innate immunity in the development of inflammatory and autoimmune diseases. Ann NY Acad Sci. 2005;1051:787–98.PubMedCrossRefGoogle Scholar
  45. 45.
    Smith PD, Smythies LE, Mosteller-Barnum M, Sibley DA, Russell MW, Merger M, et al. Intestinal macrophages lack CD14 and CD89 and consequently are down-regulated for LPS- and IgA-mediated activities. J Immunol. 2001;167:2651–6.PubMedGoogle Scholar
  46. 46.
    Smith PD, Ochsenbauer-Jambor C, Smythies LE. Intestinal macrophages: unique effector cells of the innate immune system. Immunol Rev. 2005;206:149–59.PubMedCrossRefGoogle Scholar
  47. 47.
    Rogler G, Andus T, Aschenbrenner E, Vogl D, Falk W, Scholmerich J, et al. Alterations of the phenotype of colonic macrophages in inflammatory bowel disease. Eur J Gastroenterol Hepatol. 1997;9:893–9.PubMedGoogle Scholar
  48. 48.
    MacDermott RP. Treatment of irritable bowel syndrome in outpatients with inflammatory bowel disease using a food and beverage intolerance, food and beverage avoidance diet. Inflamm Bowel Dis. 2007;13:91–6.PubMedCrossRefGoogle Scholar
  49. 49.
    MacDonald TT, Gordon JN. Bacterial regulation of intestinal immune responses. Gastroenterol Clin North Am. 2005;34:401–12.PubMedCrossRefGoogle Scholar
  50. 50.
    Lohr M, Kaltner H, Lensch M, Andre S, Sinowatz F, Gabius HJ. Cell-type-specific expression of murine multifunctional galectin-3 and its association with follicular atresia/luteolysis in contrast to pro-apoptic galectins-1 and -7. Histochem Cell Biol. 2008;130:567–81.PubMedCrossRefGoogle Scholar
  51. 51.
    Sano H, Hsu DK, Yu L, Apgar JR, Kuwabara I, Yamanaka T, et al. Human galectin-3 is a novel chemoattractant for monocytes and macrophages. J Immunol. 2000;165:2156–64.PubMedGoogle Scholar
  52. 52.
    André S, Sanchez-Ruderisch H, Nakagawa H, Buchholz M, Koptiz J, Forberich P, et al. Tumor suppressor p16INK4a–modulator of glycomic profile and galectin-1 expression to increase susceptibility to carbohydrate-dependent induction of anoikis in pancreatic carcinoma cells. FEBS J. 2007;272:3233–56.CrossRefGoogle Scholar
  53. 53.
    Schwartz-Albiez R. Inflammation and glycosciences. In: Gabius HJ, editor. The sugar code. Fundamentals of glycosciences. Weinheim: Wiley; 2009 (in press).Google Scholar
  54. 54.
    Sharma U, Pokharel S, van Brakel TJ, van Berlo JH, Cleutjens JPM, Schroen B, et al. Galectin-3 marks activated macrophages in failure-prone hypertrophied hearts and contributes to cardiac dysfunction. Circulation. 2004;110:3121–8.PubMedCrossRefGoogle Scholar

Copyright information

© Birkhäuser Verlag, Basel/Switzerland 2009

Authors and Affiliations

  • Lenka Frol’ová
    • 1
  • Karel SmetanaJr
    • 3
  • Dana Borovská
    • 1
  • Andrea Kitanovičová
    • 1
  • Klára Klimešová
    • 1
  • Ivana Janatková
    • 4
  • Karin Malíčková
    • 4
  • Milan Lukáš
    • 4
    • 8
  • Pavel Drastich
    • 5
  • Zdeněk Beneš
    • 6
  • Ludmila Tučková
    • 1
  • Joachim C. Manning
    • 7
  • Sabine André
    • 7
  • Hans-Joachim Gabius
    • 7
  • Helena Tlaskalová-Hogenová
    • 1
    • 2
  1. 1.Department of Immunology and Gnotobiology, Institute of MicrobiologyAcademy of Sciences of the Czech Republic, v.v.i.Prague 4Czech Republic
  2. 2.1st Faculty of MedicineCharles UniversityPrague 2Czech Republic
  3. 3.Institute of Anatomy and Center of Cell Therapy and Tissue Repair, 1st Faculty of MedicineCharles UniversityPrague 2Czech Republic
  4. 4.Institute of Clinical Biochemistry and Laboratory Diagnostics, General Faculty Hospital, 1st Faculty of MedicineCharles UniversityPrague 2Czech Republic
  5. 5.Department of Gastroenterology and HepatologyInstitute of Clinical and Experimental MedicinePrague 4Czech Republic
  6. 6.2nd Internal ClinicTeaching Thomayer HospitalPrague 4Czech Republic
  7. 7.Institute of Physiological Chemistry, Faculty of Veterinary MedicineLudwig-Maximilians-UniversityMunichGermany
  8. 8.IBD Clinical and Research Centre, ISCARE IVFPrague 7Czech Republic

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