INDUCTION OF ACUTE GASTRITIS AND EPITHELIAL APOPTOSIS BY HELICOBACTER-PYLORI LIPOPOLYSACCHARIDE

Background: The preservation of gastric mucosal homeostasis is a compl ex biologic process, controlled by a dynamic equilibrium of cell loss by apoptosis with that of cellular proliferation, and its abrogation i s a prominent feature of Helicobacter pylori-associated gastritis. In this report, we show that H. pylori lipopolysaccharide induces histolo gic lesions typical of acute gastritis and that these changes are refl ected in the increased epithelial cell apoptosis. Methods: The experim ents were conducted with groups of rats subjected to intragastric surf ace epithelial application of the lipopolysaccharide at 50 and 200 mu g per animal. The histologic assessment of the mucosal tissue and quan tification of apoptotic epithelial cells was performed 2 and 10 days a fter the lipopolysaccharide treatment. Results: Histologic examination showed that H. pylori lipopolysaccharide at both doses within 2 days induced infiltration of lamina propria with lymphocytes and plasma cel ls, edema, hyperemia, and hemorrhage extending from the lamina propria to the surface of mucosa, and the effect persisted beyond the 10 days . The in situ DNA fragmentation assay showed that lipopolysaccharide c aused a marked increase in epithelial cell apoptosis, with the numerou s apoptotic cells present not only in the superficial epithelium but a lso deeper in the glands. The mean apoptotic index in the mucosa was 5 9% when assessed 2 days after the administration of the 50-mu g lipopo lysaccharide dose and 71.9% after the 200-mu g dose, whereas in the se ctions assessed 10 days after the lipopolysaccharide treatment the apo ptotic index averaged 46% for a 50-mu g dose and 76.8% for a 200-mu g dose. Moreover, the apoptotic index showed positive correlation (r = 0 .71) with the grade of the induced inflammatory changes. Conclusions: Our findings demonstrate that H. pylori lipopolysaccharide can cause g astric mucosal responses typical of acute gastritis and identify the l ipopolysaccharide as a virulence factor responsible for the induction of gastric epithelial cell apoptosis by H. pylori.