6th Annual BMRP Investigator Meeting - Abstract
Paraepithelial Passage of Adherent Luminal Bacteria and Activation of Intestinal Macrophages in Crohn’s Disease
Katrin Menzel1, Claudia Hofmann1, Florian Obermeier1, Josef Schröder2, Werner Falk1, Jurgen Scholmerich1, Gerhard Rogler3,a
1 Departments of Internal Medicine I and 2 Pathology, University of Regensburg (Germany); 3Division of Gastroenterology and Hepatology, Department of Internal Medicine, University Hospital of Zürich (Switzerland)
Among polygenetic (e.g., NOD2/CARD15) and environmental factors the intestinal microflora seems to play an essential role in the pathogenesis of Crohn’s Disease (CD). We investigated bacterial translocation as well consecutive activation of intestinal macrophages (IMACs) in CD mucosa. The intestinal mucus layer of CD-patients showed a strong bacterial colonisation while in control patients no bacteria were detected. Translocation of adhesive bacteria (or their products) in CD was proven by accumulation of endotoxin in the intestinal tissue with remarkably differences in patients carrying heterozygous NOD2/CARD15 mutations (NOD2/CARD15 SNP8 and SNP13 > SNP12 and wildtype gene). Mucosa of CD patients with NOD2 variants contained significantly increased numbers of NF-kappaB(p65) positive cells in comparison to WT CD patients. Positive stained cells were most prominent in areas around the crypts. LPMNCs isolated from CD mucosa showed an increased oxidative burst reaction and radical production as compared to controls. The data point to an increased translocation of bacteria or bacterial products in CD patients carrying NOD2 variants finally (however, due to the NOD2 defect not initially) leading to increased activation of IMACs.
aPrincipal Investigator
Katrin Menzel1, Claudia Hofmann1, Florian Obermeier1, Josef Schröder2, Werner Falk1, Jurgen Scholmerich1, Gerhard Rogler3,a
1 Departments of Internal Medicine I and 2 Pathology, University of Regensburg (Germany); 3Division of Gastroenterology and Hepatology, Department of Internal Medicine, University Hospital of Zürich (Switzerland)
Among polygenetic (e.g., NOD2/CARD15) and environmental factors the intestinal microflora seems to play an essential role in the pathogenesis of Crohn’s Disease (CD). We investigated bacterial translocation as well consecutive activation of intestinal macrophages (IMACs) in CD mucosa. The intestinal mucus layer of CD-patients showed a strong bacterial colonisation while in control patients no bacteria were detected. Translocation of adhesive bacteria (or their products) in CD was proven by accumulation of endotoxin in the intestinal tissue with remarkably differences in patients carrying heterozygous NOD2/CARD15 mutations (NOD2/CARD15 SNP8 and SNP13 > SNP12 and wildtype gene). Mucosa of CD patients with NOD2 variants contained significantly increased numbers of NF-kappaB(p65) positive cells in comparison to WT CD patients. Positive stained cells were most prominent in areas around the crypts. LPMNCs isolated from CD mucosa showed an increased oxidative burst reaction and radical production as compared to controls. The data point to an increased translocation of bacteria or bacterial products in CD patients carrying NOD2 variants finally (however, due to the NOD2 defect not initially) leading to increased activation of IMACs.
aPrincipal Investigator