Glycosylation & Disease

, Volume 1, Issue 4, pp 235–245 | Cite as

Altered oligosaccharide expression in ulcerative colitis with increasing grades of inflammation

  • R. F. T. McMahon
  • C. J. P. Jones
  • S. Dutt
  • R. W. Stoddart
Research Papers


Ulcerative colitis is an idiopathic chronic inflammatory condition of the large bowel associated with åbnormalities of mucin synthesis and secretion. In the present study, glycans were identified in 45 formalin-fixed, paraffin-embedded tissue samples from patients with ulcerative colitis. The tissue samples represented a spectrum of inflammation from chronic quiescent disease to severe inflammation. Thirteen biotinylated lectins, directed against a range of sialyl, fucosyl andN-acetylgalactosaminyl sequences, were applied using an avidin-peroxidase revealing system. The results were assessed semiquantitatively for a number of cellular sites. The expression of all sialyl sequences was increased in absorptive cells and in goblet cells and the expression of α2–6-linked sialyl sequences was enhanced in proportion to the degree of inflammation, while α2–3-linked sialyl sequences were diminished in more severe inflammation. The binding ofN-acetylgalactosaminyl-directed lectins was increased in the Golgi apparatus, while there was a reduction in the expression of α-fucosyl sequences in severe degrees of inflammation. This suggests that there is an increased biosynthetic rate for sialyl residues in all stages of disease with a reduction in α2–3-linked sialyl and fucosyl sequences in severe inflammation, and a shift from storedN-acetylgalactosaminyl sequences in goblet cells to an earlier form in the Golgi apparatus. The changes in sialyl sequences are a feature of ulcerative colitis even in quiescent disease and may be related to its aetiology and early pathogenesis, while most of the other changes reflect the severity of the disease and are probably part of its later pathogenesis or of induced reactive changes.

Key words

colon histochemistry lectins rectum ulcerative colitis 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Jass JR, England J, Miller K. Value of mucin histochemistry in follow up surveillance of patients with long standing ulcerative colitis.J Clin Pathol 1986:39, 393–8PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Boland CR, Lance P, Levin B, Riddell RH, Kim YS. Abnormal goblet cell glycoconjugates in rectal biopsies associated with an increased risk of neoplasia in patients with ulcerative colitis: early results of a prospective study.Gut 1984:25; 1364–71.PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Jacobs LR, Huber PW. Regional distribution and alterations of lectin binding to colorectal mucin in mucosal biopsies from controls and subjects with inflammatory bowel disease.J Clin Invest 1985:75; 112–18.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Pihl E, Peura A, Johnson WR, McDermott FT, Hughes ESR. T-antigen expression by peanut agglutinin staining relates to mucosal dysplasia in ulcerative colitis.Dis Colon Rectum 1985:28; 11–17.PubMedCrossRefGoogle Scholar
  5. 5.
    Forzard JBJ, Dixon MF, Axon ATR, Giles GR. Lectin and mucin histochemistry as an aid to cancer surveillance in ulcerative colitis.Histopathology 1987:11; 385–94.CrossRefGoogle Scholar
  6. 6.
    Ahnen DJ, Warren GH Greene LJ, Singleton JW, Brown WR. Search for a specific marker of mucosal dysplasia in chronic ulcerative colitis.Gastroenterology 1987:93; 1346–55.PubMedGoogle Scholar
  7. 7.
    Cooper HS, Farano P, Coapman RA. Peanut lectin binding sites in colons of patients with ulcerative colitis.Arch Pathol Lab Med 1987:111; 270–5.PubMedGoogle Scholar
  8. 8.
    Rhodes JM, Black RR, Savage A. Altered lectin binding by colonic epithelial glycoconjugates in ulcerative colitis and Crohn's disease.Dig Dis Sci 1988:33; 1359–63.PubMedCrossRefGoogle Scholar
  9. 9.
    Shah M, Shrikhande SS, Swaroop VS. Lectin binding in colorectal mucosa.Ind J Gastroenterol 1989:8; 31–3.Google Scholar
  10. 10.
    Yoshioka H, Inada M, Ogawa K, et al. Lectin histochemistry in ulcerative colitis and Crohn's disease.J Exp Pathol 1989:4; 69–78.PubMedGoogle Scholar
  11. 11.
    Xu H, Sakamoto K, Shamsuddin AM. Detection of the tumor marker D-galactose-β-(1–3)-N-Acetyl-D-galactosamine in colonic cancer and pre-cancer.Arch Pathol Lab Med 1992:116 1234–8.PubMedGoogle Scholar
  12. 12.
    Ryder SD, Parker, N, Ecclestone D, Haqqani MT, Rhodes JM. Peanut lectin stimulates proliferation in colonic explants from patients with inflammatory bowel disease and colon polyps.Gastroenterology 1994:106; 117–24.PubMedGoogle Scholar
  13. 13.
    Yonezawa S, Nakamura T, Tanaka S, Kuroki K, Sato E. Lectin histochemistry in a case of ulcerative colitis complicating rectal carcinoma.Acta Pathol Jpn 1985:35; 1571–9.PubMedGoogle Scholar
  14. 14.
    Jones CJP, Morrison CA, Stoddart RW. Histochemical analysis of rat testicular glycoconjugates (1) Subsets of N-linked saccharides in seminiferous tubules.Histochem J 1992:24; 319–26.PubMedCrossRefGoogle Scholar
  15. 15.
    Shibuya N, Goldstein IJ, Broekaert WF, et al. The elderberry (Sambucus nigra L.) bark lectin recognises the Neu5Ac(α2,6)Gal/GalNAc sequence.J Biol Chem 1987:262; 1596–601.PubMedGoogle Scholar
  16. 16.
    Miller RL, Collawn JF, Fish WW. Purification and macromolecular properties of a sialic acid-specific lectin from the slugLimax flavus.J Biol Chem 1982:257; 7574–80.PubMedGoogle Scholar
  17. 17.
    Knibbs RN, Osborne SE, Glick GD, Goldstein IJ. Binding determinants of the sialic acid-specific lectin from the slugLimax flavus.J Biol Chem 1993:268; 18524–31.PubMedGoogle Scholar
  18. 18.
    Wang W-C, Cummings RD. The immobilized leukoagglutinin from the seeds ofMaackia amurensis binds with high affinity to complex-type Asn-linked oligosaccharides containing terminal sialic acid-linked α-2,3 to penultimate galactose residues.J Biol Chem 1988:263; 4576–85.PubMedGoogle Scholar
  19. 19.
    Lotan R, Sharon N. Peanut (Arachis hypogaea) agglutinin.Methods Enzymol 1978:50; 361–7.PubMedCrossRefGoogle Scholar
  20. 20.
    Sueyoshi S, Tsuji T, Osawa T. Carbohydrate-binding specificities of five lectins that bind to O-glycosyllinked carbohydrate chains. Quantitative analysis by frontal-affinity chromatography.Carbohydrate Res 1988:178; 213–24.CrossRefGoogle Scholar
  21. 21.
    Hindsgaul O, Norberg T, Le Pendu J, Lemieux RU. Synthesis of type 2 human blood-group antigenic determinants. The H, X, and Y haptens and variations of the H type 2 determinant as probes for the combining site of the lectin I of Ulex europaeus.Carbohydr Res 1982:109; 109–42.PubMedCrossRefGoogle Scholar
  22. 22.
    Pereira MEA, Kisailus EC, Gruezo F, Kabat EA. Immunochemical studies on the combining site of the blood group H-specific lectin I fromUlex europeus seeds.Arch Biochem Biophys 1978:185; 108–15.PubMedCrossRefGoogle Scholar
  23. 23.
    Debray H, Decout D, Strecker G, Spik G, Montreuil J. Specificity of twelve lectins towards oligosaccharides and glycopeptides related to N-glycosyl proteins.Eur J Biochem 1981:117; 41–55.PubMedCrossRefGoogle Scholar
  24. 24.
    Wood C, Kabat EA, Ebisu S, Goldstein IJ. An immunochemical study of the combining sites of the second lectin isolated from Bandeiraea simplicifolia (BS II).Ann Immunol 1978:129; 143–58.Google Scholar
  25. 25.
    Trowbridge IS. Isolation and chemical characterization of a mitogenic lectin fromPisum sativum.J Biol Chem 1974:249; 6004–12.PubMedGoogle Scholar
  26. 26.
    Pereira MEA, Kabat, EA. Immunochemical studies on the specificity of soybean agglutinin.Carbohydrate Res 1974:37; 89–102.CrossRefGoogle Scholar
  27. 27.
    Bhattacharyya L, Haraldsson M, Brewer CF. Precipitation of galactose-specific lectins by complex-type oligosaccharides and glycopeptides: studies with lectins from Ricinus communis (agglutinin I), Erythrina indica, Erythrina arborescens, Abrus precatorius (agglutinin), and Glycine max (soybean).Biochemistry 1988:27; 1034–41.PubMedCrossRefGoogle Scholar
  28. 28.
    Etzler ME, Kabat EA. Purification and characterization of a lectin (plant agglutinin) with blood group A specificity fromDolichos biflorus.Biochemistry 1970:9; 869–77.PubMedCrossRefGoogle Scholar
  29. 29.
    Baker DA, Sugii S, Kabat EA, et al. Immunochemical studies on the combining sites of Forssman hapten reactive hemagglutinins from Dolichos biflorus, Helix pomatia, and Wistaria floribunda.Biochemistry 1983:22; 2741–50.PubMedCrossRefGoogle Scholar
  30. 30.
    Tollefsen SE, Kornfeld R. Isolation and characterization of lectins from Vicia villosa. Two distinct carbohydrate binding activities are present in seed extracts.J Biol Chem 1983:258; 5165–71.PubMedGoogle Scholar
  31. 31.
    Sugii S, Kabat EA. Immunochemical specificity of the combining site ofWisteria floribunda hemagglutinin.Biochemistry 1980:19; 1192–9.PubMedCrossRefGoogle Scholar
  32. 32.
    Hammarstrom S, Kabat EA. Studies on specificity and binding properties of the blood group A reactive hemagglutinin from Helix pomatia.Biochemistry 1971:10; 1684–92.PubMedCrossRefGoogle Scholar
  33. 33.
    Jones CJP, Mosley SM, Jeffrey IJM, Stoddart RW. Elimination of the non-specific binding of avidin to tissue sections.Histochem J 1987:19; 264–8.PubMedCrossRefGoogle Scholar
  34. 34.
    McMahon RFT, Panesar MJR, Stoddart RW Glycoconjugates of the normal human colorectum.Histochem J 1994:26; 504–18.PubMedCrossRefGoogle Scholar
  35. 35.
    Sato A, Spicer SS. Ultrastructural visualisation of galactosyl residues in various alimentary epithelial cells with the peanut lectin-horseradish peroxidase procedure.Histochemistry 1982:73; 607–24.PubMedCrossRefGoogle Scholar
  36. 36.
    Roth J. Cytochemical localization of terminal N-acetyl-D-galactosamine residues in cellular compartments of intestinal goblet cells.J Cell Biol 1984:98; 399–406.PubMedCrossRefGoogle Scholar
  37. 37.
    Cooper HS, Malecha MJ, Bass, C, Fagel PL, Steplewski Z. Expression of blood group antigens H-2, Le(y) and sialylated-Le(a) in human colorectal carcinoma. An immunohistochemical study using double-labeling techniques.Am J Pathol 1991:138; 103–10.PubMedCentralPubMedGoogle Scholar
  38. 38.
    Allen DC, Foster H, Orchin JC, Biggart JD. Immunohistochemical staining of colorectal tissues with monoclonal antibodies to ras oncogene product p21 product and carbohydrate determinant antigen 19–9.J Clin Pathol 1987:40; 157–62.PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Cooper HS, Steplewski Z. Immunohistologic study of ulcerative colitis with monoclonal antibodies against tumor-associated and/or differentiation antigens.Gastroenterology 1988:93; 686–93.Google Scholar

Copyright information

© Rapid Communications of Oxford Ltd 1994

Authors and Affiliations

  • R. F. T. McMahon
    • 1
  • C. J. P. Jones
    • 1
  • S. Dutt
    • 2
  • R. W. Stoddart
    • 1
  1. 1.Divisions of Histopathology and Molecular Pathology, Department of Pathological SciencesUniversity of ManchesterManchesterUK
  2. 2.Department of HistopathologyBury General HospitalBuryUK

Personalised recommendations