Analysis for the mechanism of gastric mucosal damage by Helicobacter pylori infection

在幽门螺杆菌的多种毒力因子中，黏附因子、空泡毒素(VT)、细胞因子(尤其是白介素8(IL-8))、热休克蛋白(HSP)和活性氧是幽门螺杆菌感染致胃粘膜损伤的重要因素。此外，幽门螺杆菌对豚鼠、兔、人、羊、鸡、马和牛的红细胞具有血凝(HA)活性。幽门螺杆菌的HA活性可能与其对胃细胞的黏附活性有关。幽门螺杆菌约有一半的菌株产生VT，产生VT的菌株的培养上清液对豚鼠壁细胞的胃酸分泌有抑制作用，而不产生VT的菌株的培养上清液对胃酸的分泌没有抑制作用。通过对胃酸分泌信号转导中的第二信使(Ca^和lt；2&gt；和环磷酸腺苷)的分析，它是…S进一步提出，VT可能直接抑制质子泵H^-K^-ATPase。结果表明，幽门螺杆菌与胃上皮细胞黏附后，可诱导胃上皮细胞分泌IL-8。类似地，研究表明，人外周中性粒细胞与幽门螺杆菌共同孵育会产生活性氧(超氧化物)。然而，幽门螺杆菌菌株的培养上清液既不能诱导IL-8，也不能诱导活性氧。免疫印迹法检测10株幽门螺杆菌Hsp60(相对分子质量60 kDa)。另一方面，在流式细胞仪分析中，HSP60在Hp表面的表达在不同的Hp菌株之间存在差异。此外，HSP60在幽门螺杆菌表面的表达与菌株的黏附活性有关。在胃上皮细胞表面检测到与抗幽门螺杆菌HSP60单抗反应的表位，提示HSP60可能是胃组织慢性炎症或粘膜损伤的诱因，提示黏附因子、VT、细胞因子、活性氧和HSP60与胃粘膜损伤的发生密切相关，其机制是多因素的。较少

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 … More 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. Less