Gesteigerter enterozytärer Antigentransport über Vesikel aus dem Trans-Golgi-Netzwerk bei Morbus Crohn und Colitis ulcerosa

Abstract

Introduction: Increased transepithelial transport of luminal antigen may contribute to an increased transcellular permeability in Crohn’s disease (CD) and ulcerative colitis (UC). The aim of this study was to investigate the role of the trans-Golgi network in the transcellular transport of luminal applied ovalbumin (OVA) in normal enterocytes (NE) and in enterocytes characterized by rapid antigen uptake into the cytosol (RACE), which have been described in [1]. Methods: Tissue samples of 5 patients with CD (ileum), 5 patients with UC (colon) and 10 healthy controls without inflammatory diseases (ileum, n = 5; colon, n = 5) were incubated with the antigen ovalbumin (OVA) immediately after surgical resection. For immunoelectron microscopy, the trans-Golgi network was labeled with ulex europaeus agglutinin (UEA I). To detect quantitative differences in transcellular antigen transport between CD, UC (RACE versus NE) and healthy control the ratio of OVAloaded trans-Golgi vesicles in relation to the total number of trans-Golgi vesicles was measured per area cytosol (chi-square test). Furthermore, the labeling density of OVA within trans-Golgi vesicles was evaluated (Wilcoxon U-test). Results: In RACE, the ratio of OVA-loaded trans-Golgi vesicles was significantly higher than in NE (CD, p < 0.01; UC, p < 0.05). The lowest ratio of OVA-loaded trans-Golgi vesicles was found in healthy controls. Significantly less OVA-loaded trans-Golgi vesicles were demonstrated in healthy ileum controls compared to NE of CD and in healthy colon controls compared to NE of UC (p < 0.01 in each case). Additionally, in CD labeling density for OVA was significantlyhigher in trans-Golgi vesicles of RACE compared to NE (p < 0.05). Conclusion: In CD, UC and healthy controls the trans-Golgi network is involved in the transcellular transport of antigens through enterocytes. An increased accumulation of OVA-loaded trans-Golgi vesicles in CD and UC (RACE > NE) suggests an increase in transcellular transport processes, which may lead to an impaired epithelial barrier function.