MECHANISM OF HELICOBACTER-PYLORI PATHOGENESIS - FOCUS ON MUCUS

Although the clinical data provide increasingly convincing indications that Helicobacter pylori (H. pylori) is a causative factor in gastritis and peptic ulcer, the advances toward the clear understanding of this bacterium's pathogenic action are slow in coming. Having a niche bordering two major perimeters of gastric mucosal defense, H. pylori is capable of exerting detrimental effects on the mucus layer, as well as surface cells of the gastric epithelium. To cause such an effect, the bacteria must first, however, attach to the mucosa. Our findings indicate that this attachment involves specific structures on the epithelial cell surfaces, namely lactosylceramide sulfate and GM3 ganglioside. The analysis of the glycolipid distribution pattern in different regions of human stomach revealed that the antral mucosal content of GM3 and lactosylceramide sulfate are considerably higher than that of the fundus, which may account for the prevalence of H. pylori colonization of the antrum. We have also established that H. pylori causes considerable untoward changes in gastric mucus coat integrity. These changes are reflected in the loss of protective qualities of mucus due to the action of H. pylori-elaborated proteases and lipases. The result of H. pylori protease action is disintegration of the polymeric structure of mucin, whereas the elaborated lipases and phospholipase A2 in particular result in mucus lipid degradation, loss of mucosal surface, hydrophobicity, and lysophospholipid generation. The lytic activity of the resulting lysophospholipids is detrimental not only to mucus gel integrity, but even more so to the cell membrane of gastric epithelium. Although the pathogenic consequences of H. pylori colonization of gastric mucosa almost certainly result from many facets, the findings that mucosal attachment and the mucolytic enzymes elaborated by the bacterium are subject to inhibition by certain mucosal strengthening agents could aid in a more rational approach to H. pylori-associated gastric disease.