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，粘附因子、空泡毒素（vacuolating toxin，VT）、细胞因子（特别是白细胞介素8（interleukin-8，IL-8））、热休克蛋白（heat shock protein，HSP）和活性氧（active oxygen）是幽门螺杆菌感染胃粘膜损伤的主要毒力因子，流式细胞术（flowcytometric，FCM）分析表明，幽门螺杆菌对胃上皮细胞的粘附作用强于肠上皮细胞。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。幽门螺杆菌菌株的HA活性可能与其对胃细胞的粘附活性相关。约有一半的H.pylori菌株产生VT。VT产生菌株的培养上清抑制豚鼠壁细胞的胃酸分泌，而VT不产生菌株的培养上清则无此作用。通过对胃酸分泌信号转导中第二信使Ca^<2+>和cAMP的分析，发现胃酸分泌信号转导中的第二信使Ca^<2+>和cAMP与胃酸分泌有关， ...更多信息 提示VT可直接抑制质子泵H^+-K^+-ATP酶。结果表明，幽门螺杆菌在粘附于胃上皮细胞后诱导胃上皮细胞分泌IL-8。类似地，证明了人外周中性粒细胞与幽门螺杆菌的共孵育导致活性氧（超氧化物）的产生。然而，幽门螺杆菌菌株的培养上清液既不诱导IL-8也不诱导活性氧。HSP 60（分子量：60 kDa）在10株幽门螺杆菌中均被检测到。另一方面，流式细胞术分析显示，H.pylori表面HSP 60的表达在不同的H.pylori菌株中存在差异。此外，HSP 60在细胞表面的表达率与H.pylori菌株的粘附活性相关。在胃上皮细胞表面检测到与H.pylori HSP 60单克隆抗体反应的抗原表位，提示HSP 60可能是胃组织慢性炎症或粘膜损伤的触发因子，提示粘附因子、VT、细胞因子、活性氧和HSP 60均与胃粘膜损伤的发生密切相关，并且粘膜损伤的机制是多因素的。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