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Störung des HLA-vermittelten Antigentransports in Enterozyten von Patienten mit chronisch-entzündlichen Darmerkrankungen

  • Markus Utech
  • Ö. Kalem
  • S. Kersting
  • M. Brüwer
  • K.-P. Zimmer
  • N. Senninger
  • G. Schürmann
  • C. F. Krieglstein
Conference paper
Part of the Deutsche Gesellschaft für Chirurgie book series (DTGESCHIR, volume 31)

Abstract

Introduction: The pathogenesis of inflammatory bowel disease (IBD; e.g. ulcerative colitis (UC) and Crohn‘s disease, CD) is still unknown. Recent reports suggest a possible disorder of oral tolerance caused by a dysfunctional MHC regulated antigen presentation of enterocytes to lymphocytes of the mucosa-associated lymphatic system (MALT). Therefore the objective of our study was to investigate the intracellular MHC distribution of enterocytes of patients with IBD and compare them with enterocytes of a healthy control group (CG). In IBD-patients both regular enterocytes (NE) and enterocytes with cytosolic antigen intake (RACE, rapid antigen uptake into the cytosol enterocytes) were examined in this case. Method: Fresh mucosal specimens of MC (ileum [il]), CU (colon [co]) patients and controls (CG-ileum, CG-colon, each n = 5) were incubated with egg albumin antigen (OVA). Following MHC-DP, -DQ, -DR (MHC-II) and OVA as well as β 2-microglobulin, a structure protein of MHC-I and OVA were localized using an immunogold double-labeling method with mono- and polyclonal antibodies by electron microscopy. Distinguished between antigen-loaded and antigen-free MHC-positive vesicles the number of this vesicle per cut cell face were determined. As a measure of the concentration of MHC-I being in the rough endoplasmic reticulum (RER) the number of gold points were counted per membrane length. Statistical analysis was performed using χ2- or Fischer‘s exact test with p < 0.05 considered significant. Results: Compared to control group normal enterocytes of patients with MC and CU showed a significantly stronger enrichment of antigen-loaded (MC: 22.7 ± 8.8 vs. 2.1 ± 1.9; CU: 70.8 ± 15.3 vs. 0) and antigen-free (MC: 32.1 ± 10.9 vs. 14.6 ± 6.5; CU: 54.1 ± 17.5 vs. 6.2 ± 5.0) vesicles. In contrast to that the MHC-II-positive vesicles were significantly reduced at RACE of MC (2.8 ±2.4) and CU (25.5 ±8.1) compared with NE as well as compared to CG-enterocytes. In the RER of RACE a significant stronger expression of MHC-I (MC: 30.3 ±6.1; CU: 24.3 ± 4.7) were found compared to control enterocytes (MC: 6.9 ± 2.1; CU: 11.2 ± 3.5) and NE (MC: 2.1 ± 0.6; CU: 1.5 ± 0.5) of MC and CU. Conclusion: The decrease of antigen presentation provided by MHC-II proteins in RACE cells at simultaneous activation of MHC-I proteins in the RER possibly represents a morphological correlative for a changed oral tolerance in patients with IBD.

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Literatur

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Copyright information

© Springer-Verlag Berlin Heidelberg 2002

Authors and Affiliations

  • Markus Utech
    • 1
    • 3
  • Ö. Kalem
    • 1
  • S. Kersting
    • 1
  • M. Brüwer
    • 1
  • K.-P. Zimmer
    • 2
  • N. Senninger
    • 1
  • G. Schürmann
    • 1
  • C. F. Krieglstein
    • 1
  1. 1.Klinik und Poliklinik für Allgemeine ChirurgieGermany
  2. 2.Klinik und Poliklinik für KinderheilkundeUniversitätsklinikum MünsterGermany
  3. 3.Klinik und Poliklinik für Allgemeine ChirurgieUniversitätsklinikum MünsterMünsterGermany

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