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Expression of ICAM-1 in colon epithelial cells: an ultrastructural study performed on in vivo and in vitro models

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Abstract

Background

Studies have suggested that in ulcerative colitis (UC), intercellular adhesion molecule-1 (ICAM-1) is involved in migration of leukocytes toward the colonic epithelium. A suitable in vitro model of chronic colonic inflammation does not exist, and the role of the epithelium is based on monolayers of cancer cells. Conflicting results exist on epithelial ICAM-1 expression, and the aim of this study was to compare the expression in various models of colonic epithelium.

Materials and methods

Colonic biopsies from four UC patients and four controls were examined by cryoimmuno-electron microscopy using ICAM-1-antibodies. In four other controls, the epithelium was isolated from colonic biopsies, embedded in collagen, and evaluated similarly. Isolated crypts and cultured cancer cells were stimulated with interferon-γ (IFN-γ) or tumor necrosis factor-α (TNF-α).

Results

ICAM-1 was not expressed in the biopsies. In contrast, HT29 cells and the collagen-embedded crypts expressed ICAM-1 on the apical membranes proximal to the junctional complexes when stimulated with IFN-γ or TNF-α in a dose-related manner.

Conclusions

ICAM-1 is not expressed on colonic epithelium in vivo. However, both colonocytes and HT29 cells were capable of expressing ICAM-1 on their apical membranes in response to supraphysiologic cytokine concentrations. These observations question the justification of extrapolating observations from colon cancer cell lines to in vivo inflammatory conditions.

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References

  1. Agace WW, Patarroyo M, Svensson M, Carlemalm E, Svanborg C (1995) Escherichia coli induces transuroepithelial neutrophil migration by an intercellular adhesion molecule-1-dependent mechanism. Infect Immun 63:4054–4062

    CAS  PubMed  Google Scholar 

  2. Allan RN, Rhodes JM, Hanauer SB, Keighley MRB, Alexander-Williams J, Fazio VW (1997) Inflammatory bowel diseases, 3rd edn. Churchill Livingstone, New York

  3. Bloom S, Simmons D, Jewell DP (1995) Adhesion molecules intercellular adhesion molecule-1 (ICAM-1), ICAM-3 and B7 are not expressed by epithelium in normal or inflamed colon. Clin Exp Immunol 101:157–163

    Google Scholar 

  4. Capobianchi MR, Fais S, Di Paolo MC, Agostini D, Paoluzi P, Pallone F, et al (1992) Absence of circulating interferon in patients with inflammatory bowel disease. Suggestion against an autoimmune etiology. Clin Exp Immunol 90:85–87

    CAS  PubMed  Google Scholar 

  5. Colgan SP, Parkos CA, Delp C, Arnaout MA, Madara JL (1993) Neutrophil migration across cultured intestinal epithelial monolayers is modulated by epithelial exposure to IFN-gamma in a highly polarized fashion. J Cell Biol 120:785–798

    CAS  PubMed  Google Scholar 

  6. De Vos M, Verdievel H, Schoonjans R, Praet M, Bogaert M, Barbier F (1992) Concentrations of 5-ASA and Ac-5-ASA in human ileocolonic biopsy homogenates after oral 5-ASA preparations. Gut 33:1338–1342

    PubMed  Google Scholar 

  7. Dippold W, Wittig B, Schwaeble W, Mayet W, Meyer zum Büschenfelde K-H (1993) Expression of intercellular adhesion molecule 1 (ICAM-1, CD54) on colonic epithelial cells. Gut 34:1593–1597

    CAS  PubMed  Google Scholar 

  8. Gao J-X, Wilkins J, Issekutz AC (1995) Migration of human polymorphonuclear leukocytes through a synovial fibroblast barrier is mediated by both β2 (CD11/CD18) integrins and the β1 (CD29) integrins VLA-5 and VLA-6. Cell Immunol 163:178–186

    Article  CAS  PubMed  Google Scholar 

  9. Jones SC, Banks RE, Haidar A (1995) Adhesion molecules in inflammatory bowel disease. Gut 36:724–730

    CAS  PubMed  Google Scholar 

  10. Kaiserlian D, Rigal D, Abello J, Revillard JP (1991) Expression, function and regulation of the intercellular adhesion molecule-1 (ICAM-1) on human epithelial cell lines. Eur J Immunol 21:2415–2421

    CAS  PubMed  Google Scholar 

  11. Komatsu M, Kobayashi D, Saito K, Furuya D, Yagihashi A, Araake H, et al (2001) Tumor necrosis factor-α in serum of patients with inflammatory bowel disease ad measured by a highly sensitive immuno-PCR. Clin Chem 47:1297–1301

    CAS  PubMed  Google Scholar 

  12. Kvale D, Krajci P, Brandtzaeg P (1992) Expression and regulation of adhesion molecules ICAM-1 (CD54) and LFA-3 (CD58) in human intestinal epithelial cell lines. Scand J Immunol 35:669–686

    CAS  PubMed  Google Scholar 

  13. Larson RS, Springer TA (1990) Structure and function of leukocyte integrins. Immunol Rev 114:181–217

    CAS  PubMed  Google Scholar 

  14. Malizia G, Calabrese A, Cottone M, Raimondo M, Trejdosiewicz LK, Smart CJ, et al (1991) Expression of leukocyte adhesion molecules by mucosal mononuclear phagocytes in inflammatory bowel disease. Gastroenterology 100:150–159

    PubMed  Google Scholar 

  15. Mishra L, Mishra BB, Harris M, Bayless TM, Muchmore AV (1994) In vitro cell aggregation and cell adhesion molecules in Crohn’s disease. Clin Exp Immunol 96:432–436

    PubMed  Google Scholar 

  16. Morise K, Yamaguchi T, Kuroiwa A (1994) Expression of adhesion molecules and HLA-DR by macrophages and dendritic cells in aphtoid lesions in Crohn’s disease: an immunocytochemical study. J Gastroenterol 29:257–264

    CAS  PubMed  Google Scholar 

  17. Nakamura S, Ohtani H, Watanabe Y, Fukushima K, Matsumoto T, Kitano A, et al (1993) In situ expression of the cell adhesion molecules in inflammatory bowel disease: evidence of immunologic activation of vascular endothelial cells. Lab Invest 69:77–85

    CAS  PubMed  Google Scholar 

  18. Nielsen OH, Brynskov J, Bendtzen K (1993) Circulating and mucosal concentrations of tumour necrosis factor and inhibitor(s) in chronic inflammatory bowel disease. Dan Med Bull 40:247–249

    CAS  PubMed  Google Scholar 

  19. Oshitani N, Campbell A, Bloom S, Kitano A, Kobayashi K, Jewell DP (1995) Adhesion molecule expression on vascular endothelium and nitroblue titrazolium reducing activity in human colonic mucosa. Scand J Gastroenterol 30:915–920

    CAS  PubMed  Google Scholar 

  20. Parkos CA, Colgan SP, Diamond MS, Nusrat A, Liang TW, Springer TA, et al (1996) Expression and polarization of intercellular adhesion molecule-1 on human intestinal epithelia: consequences for CD11b/CD18-mediated interactions with neutrophils. Mol Med 2:489–505

    CAS  PubMed  Google Scholar 

  21. Pimpo MT, Frieri G, Palumbo G, Pantaleoni GC, Viscido A, Caprilli R, et al (1997) Postoperative recurrence of Crohn’s disease and 5-ASA mucosal concentration. A GISC study. Gastroenterology 112:A1061

    Google Scholar 

  22. Pober JS, Gimbrone MA, Lapierre LA, Mendrick DL, Fiers W, Rothlein R, et al (1986) Overlapping patterns of activation of human endothelial cells by interleukin-1, tumor necrosis factor and immune interferon. J Immunol 137:1893–1896

    CAS  PubMed  Google Scholar 

  23. Pooley N, Ghosh L, Sharon P (1995) Up-regulation of E-selectin and intercellular adhesion molecule-1 differs between Crohn’s disease and ulcerative colitis. Dig Dis Sci 40:219–225

    CAS  PubMed  Google Scholar 

  24. Schürmann GM, Aber-Bishop AE, Facer P, Lee JC, Rampton DS, Doré CJ, et al (1993) Altered expression of cell adhesion molecules in uninvolved gut in inflammatory bowel disease. Clin Exp Immunol 94:341–347

    Google Scholar 

  25. Seidelin JB, Jäättelä M, Nielsen OH (2003) Continuous interferon-γ or tumor necrosis factor-α stimulation of colonocytes increase cell proliferation and decrease apoptosis. Am J Gastroenterol (in press)

  26. Simmons D, Makgoba MW, Seed B (1988) ICAM, and adhesion ligand of LFA-1, is homologous to the neural cell adhesion molecule NCAM. Nature 331:624–627

    Article  CAS  PubMed  Google Scholar 

  27. Springer TA (1994) Traffic signals for lymphocyte recirculation and leukocyte migration: the multistep paradigm. Cell 76:301–314

    CAS  PubMed  Google Scholar 

  28. Sträter J, Wedding U, Barth TFE, Koretz K, Elsing C, Möller P (1996) Rapid onset of apoptosis in vitro follows disruption of β1-integrin/matrix interactions in human colonic crypt cells. Gastroenterology 110:1776–1784

    PubMed  Google Scholar 

  29. Vainer B, Nielsen OH (2000) Changed colonic profile of P-selectin, PECAM-1, ICAM-1, ICAM-2, and ICAM-3 in inflammatory bowel disease. Clin Exp Immunol 121:242–247

    CAS  PubMed  Google Scholar 

  30. Vainer B, Nielsen OH (2000) Chemotactic properties of ICAM-1 and PECAM-1 on neutrophil granulocytes in ulcerative colitis: effects of prednisolone and mesalazine. Aliment Pharmacol Ther 14:1023–1032

    Article  CAS  PubMed  Google Scholar 

  31. Vainer B, Nielsen OH, Horn T (2000) Comparative studies on the colonic in situ expression of intercellular adhesion molecules (ICAM-1, -2, and 3), β2 integrins (LFA-1, Mac-1, and p150,95), and PECAM-1 in ulcerative colitis and Crohn’s disease. Am J Surg Pathol 24:1115–1124

    PubMed  Google Scholar 

  32. Vainer B, Sørensen S, Nielsen OH, Horn T (2002) Subcellular localization of intercellular adhesion molecule-1 in colonic mucosa in ulcerative colitis. Ultrastruct Pathol 26:113–121

    Article  PubMed  Google Scholar 

  33. Whitehead RH, Brown A, Bhathal PS (1987) A method for the isolation and culture of human colonic crypts in collagen gels. In Vitro 3:436–442

    Google Scholar 

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Acknowledgements

The authors wish to thank Ms. Hanne Kruse for invaluable technical assistance as well as Jakob Hendel, MD, and Anders Perner, MD, PhD, for assistance in obtaining biopsies. Mesalazine was kindly donated by Søren Halskov, Ferring Pharmaceuticals, Copenhagen, Denmark. The study was supported by a grant from Else and Mogens Wedell-Wedellsborg’s Foundation, Denmark.

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Correspondence to Ben Vainer.

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Vainer, B., Sørensen, S., Seidelin, J. et al. Expression of ICAM-1 in colon epithelial cells: an ultrastructural study performed on in vivo and in vitro models. Virchows Arch 443, 774–781 (2003). https://doi.org/10.1007/s00428-003-0900-5

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  • DOI: https://doi.org/10.1007/s00428-003-0900-5

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