KURAZONO Hisao Okayama University, School of Health Science, Professor, 医学部, 教授 (90186487)
AOYAMA Nobuo Kobe University School of Medicine, Kobe University Hospital, Associate Professor, 医学部付属病院, 助教授 (30243299)
WADA Akihiro Nagasaki University, Institute of Tropical Medicine, Lecturer, 熱帯医学研究所, 講師 (70253698)
SHIRASAKA Daisuke Kobe University School of Medicine, Kobe University Hospital, Medical Researcher, 医学部付属病院, 医員
|Budget Amount *help
¥12,900,000 (Direct Cost : ¥12,900,000)
Fiscal Year 2003 : ¥6,000,000 (Direct Cost : ¥6,000,000)
Fiscal Year 2002 : ¥6,900,000 (Direct Cost : ¥6,900,000)
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].