Research for comparison of VacA in H. pylori infectious diseases

幽门螺杆菌的持续感染可引起慢性活动性胃炎，使粘膜易于发生消化性溃疡，并被认为参与胃癌和MALT淋巴瘤的发病机制。幽门螺杆菌分泌VacA，一种导致易感细胞空泡变性的细胞毒素。VacA中间的序列定义了两个家族，称为m1 VacA和m2 VacA，它们在细胞特异性上不同。由于s1/m2菌株产生低水平的毒素，因此很可能是m1 VacA。本研究从H. pylori分离自患有H.与m1 VacA类似，m2 VacA被酸或碱激活，从而增强其结合细胞，这是易感细胞中空泡形成的初始步骤。免疫沉淀实验表明，激活的m2 VacA与miVacA类似，在AZ-52 - 1细胞中与两种受体样蛋白酪氨酸磷酸酶RPTPa和RPTP（3）结合，提示激活的m2 VacA和m1 VacA可能参与H.幽门螺杆菌感染。我们的结果。提示m2 VacA是一个重要的毒力因子，支持H.具有m2 VacA的幽门螺杆菌菌株与Go等报道的十二指肠溃疡有关[Go，M. F.、西塞尔湖和Grayham，D. Y.（1998）Scand. J. Gastroenterol. 33，132-136]。

Persistent infection with Helicobacter pylori causes chronic active gastritis, which predisposes the mucosa to peptic ulceration, and is believed to participate in the pathogenesis of gastric carcinoma and MALT lymphoma. H pylori secretes VacA, a cytotoxin that causes vacuolar degeneration of susceptible cells. Sequence in the middle of VacA defines two families, termed m 1 VacA and m2 VacA, which differ in cell specificity. Since s1/m2 strains produce low levels of toxin, it is likely that m1VacA. is responsible for more epithelial damage than m2VacA.In this study, we purified m 1 VacA and m2VacA from culture medium from H. pylori isolated from patients suffering from H. pylori-induced various diseases in Philippine and Japan.Similar to m1VacA, m2VacA is activated by acid or alkali, thereby enhancing its binding cells, the initial step in vacuole formation in susceptible cells. Immunoprecipitation experiments showed that activated m2VacA, similar to miVacA, binds to two receptor-like protein tyrosine phosphatases, RPTPa and RPTP(3 in AZ-52 1 cells, suggesting that activated m2VacA as well as m1VacA may contribute to gastrointestinal disease following H. pylori infection.Our results. lead that m2VacA is a significant virulence factor and support the finding that H. pylori strains with m2VacA is associated with duodenal ulcer reported by Go et al. [Go, M. F., Cissell, L., and Grayham, D. Y. (1998) Scand. J. Gastroenterol. 33, 132-136].