SUCRALFATE COUNTERACTS THE INHIBITION OF GASTRIC-MUCOSAL MUCIN RECEPTOR BY HELICOBACTER-PYLORI LIPOPOLYSACCHARIDE

Background: Among the disturbances in gastric mucosal defense associat ed with Helicobacter pylori infection is the loss of mucus coat contin uity, which results in a severe disturbance in the ability of mucus co at to maintain its functions as the pre-epithelial element of gastric mucosal defense. Here, we show that H. pylori, through its cell-wall l ipopolysaccharide, disrupts the interaction between gastric mucin and its mucosal receptor, and that sucralfate is capable of counteracting this untoward effect of the bacterium. Methods: The receptor was isola ted from octylglucoside-solubilized gastric mucosal epithelial cell me mbranes by affinity chromatography on Sepharose-bound wheat germ agglu tinin and following iodination with I-125, used in the binding assays for mucin in the presence of H. pylori lipopolysaccharide and sucralfa te. Results: Preincubation of the receptor protein with H. pylori lipo polysaccharide led to a decrease in mucin binding. The inhibitory effe ct was proportional to the concentration of lipopolysaccharide and rea ched a maximum of 91% at 30 mu g/ml. The effect of H. pylori lipopolys accharide was countered by sucralfate, which caused a dose-dependent r elief of the inhibitory effect. The maximum (75%) restoration in mucin -receptor binding occurred at 60 mu g/ml sucralfate. Conclusions: The results provide strong evidence for the effectiveness of sucralfate in preventing the loss of gastric mucus coat continuity caused by H. pyl ori.