Day A S, Jones N L, Policova Z, Jennings H A, Yau E K, Shannon P, Neumann A W, Sherman P M
Division of Gastroenterology and Nutrition, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.
Dig Dis Sci. 2001 Sep;46(9):1943-51. doi: 10.1023/a:1010691216207.
Gastric infection with Helicobacter pylori results in chronic active gastritis and in some individuals is associated with complications such as peptic ulceration and gastric cancers. A balance between bacterial factors and host responses may determine disease outcome. The mouse-adapted H. pylori strain SS1 has been utilized as a model to study disease pathogenesis. Although chronic gastritis is observed in this murine model of H. pylori infection, other complications of disease seen in the human host (such as peptic ulceration) are not identified. The objectives of this study were to characterize virulence factors of the mouse-adapted H. pylori strain SS1 and determine host responses to infection. Vacuolating cytotoxin activity of H. pylori strain SS1 was determined after incubation of HEp-2 cells with culture supernatant for 24 hr. Polymerase chain reaction was performed to detect the presence of the cagA and cagE genes. Chemokine responses from human gastric epithelial cells infected with H. pylori SS1 were assessed by measurement of the concentration of interleukin-8 in cell-free supernatants. C57BL/6 and gld mice were infected with strain SS1 or sham-infected. Eight weeks following infection, gastric tissues were obtained for histological analysis and surface hydrophobicity was measured by axisymmetric drop-shape analysis. H. pylori strain SS1 was cytotoxin negative, cagA positive, and cagE positive, but induced only a modest interleukin-8 response (684 +/- 140 pg/ml) from AGS gastric epithelial cells in comparison to a clinical isolate (4170 +/- 410 pg/ml, P < 0.0005). Increased inflammation was observed in the stomachs of H. pylori strain SS1-infected animals compared to uninfected controls. Gastritis was not associated with any disease complications. Despite mucosal inflammation, infected mice did not demonstrate alterations in gastric surface hydrophobicity (42.2 degrees +/- 2.2 degrees and 41.4 degrees +/- 3.2 degrees for C57BL/6 and gld, respectively) compared to uninfected mice (43.2 degrees +/- 2.3 degrees and 39.5 degrees +/- 1.6 degrees, respectively). In conclusion, murine infection with H. pylori SS1, which contains putative bacterial virulence factors, results in gastric inflammation. However, the mucosal changes are not associated with alterations in surface hydrophobicity. Therefore, the mouse model of infection with H. pylori, strain SS1 may not serve as an entirely appropriate model to study host factors associated with disease complications.
幽门螺杆菌感染胃部会导致慢性活动性胃炎，在某些个体中还与消化性溃疡和胃癌等并发症相关。细菌因素与宿主反应之间的平衡可能决定疾病的转归。适应小鼠的幽门螺杆菌菌株SS1已被用作研究疾病发病机制的模型。尽管在这种幽门螺杆菌感染的小鼠模型中观察到了慢性胃炎，但未发现人类宿主中出现的其他疾病并发症（如消化性溃疡）。本研究的目的是鉴定适应小鼠的幽门螺杆菌菌株SS1的毒力因子，并确定宿主对感染的反应。将HEp-2细胞与培养上清液孵育24小时后，测定幽门螺杆菌菌株SS1的空泡毒素活性。进行聚合酶链反应以检测cagA和cagE基因的存在。通过测量无细胞上清液中白细胞介素-8的浓度，评估感染幽门螺杆菌SS1的人胃上皮细胞的趋化因子反应。C57BL/6和gld小鼠感染菌株SS1或进行假感染。感染8周后，获取胃组织进行组织学分析，并通过轴对称滴形分析测量表面疏水性。幽门螺杆菌菌株SS1细胞毒素阴性，cagA阳性，cagE阳性，但与临床分离株相比，仅诱导AGS胃上皮细胞产生适度的白细胞介素-8反应（684±140 pg/ml）（4170±410 pg/ml，P<0.0005）。与未感染的对照组相比，感染幽门螺杆菌菌株SS1的动物胃中炎症增加。胃炎与任何疾病并发症均无关联。尽管存在黏膜炎症，但与未感染的小鼠相比，感染的小鼠胃表面疏水性未显示出改变（C57BL/6和gld分别为42.2°±2.2°和41.4°±3.2°）（分别为43.2°±2.3°和39.5°±1.6°）。总之，感染含有假定细菌毒力因子的幽门螺杆菌SS1的小鼠会导致胃部炎症。然而，黏膜变化与表面疏水性改变无关。因此，幽门螺杆菌菌株SS1感染的小鼠模型可能不是研究与疾病并发症相关的宿主因素的完全合适的模型。
