Background: It has previously been reported that there is a strong correlation between the expression of glycosylphosphatidylinositol (GPI)-anchored complement membrane inhibitor in gastric epithelium and the severity of inflammation of gastric mucosa. To investigate the regulation of complement activity in gastric epithelium during Helicobacter pylori (H. pylori)-associated gastritis, the expression of GPI-anchored complement membrane inhibitors, decay-accelerating factor (DAF) and 20-kDa homologous restriction factor 20 (HRF20), and membrane cofactor protein (MCP), which is a transmembrane protein, were evaluated after removal of the H. pylori stimulus. Furthermore, the expression of the complement fragment, C3c, was also investigated.
Methods: Forty-six patients with epigastric symptoms and endoscopically confirmed peptic ulcer or gastritis who had H. pylori infection of the gastric mucosa were enrolled in the present study. Biopsy specimens were obtained from the gastric antrum and corpus 1 month before and after eradication. Helicobacter pylori infection was determined by the rapid urease test, histology, and culture before eradication, and by histology, culture, and urea breath test after eradication. Gastric biopsy specimens obtained before and after eradication were evaluated for infiltration by neutrophils and mononuclear cells. The expression of complement membrane inhibitors, DAF, HRF20, and MCP and that of the main complement fragment, C3c, was immunohistochemically evaluated.
Results: One month after the eradication of H. pylori, the infiltration by neutrophils and mononuclear cells in the gastric mucosa decreased significantly (P < 0.0001) as compared with that before eradication. The expression of DAF, HRF20, and C3c on gastric mucosal epithelium also significantly decreased in both the antrum and the corpus (P < 0.05) 1 month after eradication. However, no change was observed in the expression of MCP.
Conclusions: The decrease in the expression of GPI-anchored complement regulator and the complement after removal of a chronic microbial stimulus suggests that the gastric epithelium appears to undergo an aggressive stress of complement during H. pylori infection. Conclusively, DAF and HRF20 may play an important protective role against complement-mediated damage induced by chronic microbial stimuli in such a pathological condition.