|Budget Amount *help
¥2,300,000 (Direct Cost : ¥2,300,000)
Fiscal Year 1996 : ¥900,000 (Direct Cost : ¥900,000)
Fiscal Year 1995 : ¥1,400,000 (Direct Cost : ¥1,400,000)
Among various virulence factors of Helicobacter pylori, adhesion factor, vacuolating toxin (VT), cytokines (particularly, interleukin-8 (IL-8)), heat shock protein (HSP) and active oxygen were focused to analyze the mechanism of gastric mucasal damage by H.pylori infection.
According to flowcytometric (FCM) analysis, it was shown that H.pylori strains adhere more effectively to gastric epithelial cells than intestinal cells. In addition, H.pylori has hemagglutinating (HA) activity with erythrocytes of guinea pig, rabbit, human, sheep, chicken, horse and bovine. It was also demonstrated that HA activity of H.pylori strains may correlate with adhesion activity to gastric cells. About half of H.pylori strains produce VT.Culture supernates of VT-producing H.pylori strains inhibited secretion of gastric acid by guinea pig parietal cells, but that of VT-non-producing strains not. By analysis of 2nd messengers (Ca^<2+> and cyclic AMP) in signal transduction for secretion of gastric acid, it wa
s suggested that VT may directly inhibit proton pump H^+-K^+- ATPase. It was shown that H.pylori induces secretion of IL-8 by gastric epithelial cells following its adhesion to the cells. Similarly, it was demonstrated that co-incubation of human peripheral neutrophils with H.pylori resulted in a generation of active oxygen (superoxide). However, neither IL-8 nor active oxygen was induced by culture supernates of H.pylori strains. HSP60 (molecular weight ; 60kDa) was equally detected in 10 H.pylori strains examined in immunoblot analysis. On the other hand, HSP60 on the surface of H.pylori was differently expressed among H.pylori strains in FCM analysis. In addition, the expression rate of HSP60 on the surface correlated with adhesion activity of H.pylori strains. The epitope reactable with monoclonal antibody against H.pylori HSP60 was detected on the surface of gastric epithelial cells, suggesting that HSP60 might be a trigger for chronic inflammation or mucosal damage in gastric tissue.
These results indicate that adhesion factor, VT,cytokines, active oxygen and HSP60 are all closely associated with the occurrence of gastric mucosal damages, and the mechanism for the mucosal damage secms to be multifactorial.