Cutting Edge: VacA, a Vacuolating Cytotoxin ofHelicobacter pylori, Directly Activates Mast Cells for Migration and Production of Proinflammatory Cytokines

作者: Volaluck Supajatura , Hiroko Ushio , Akihiro Wada , Kinnosuke Yahiro , Ko Okumura

DOI: 10.4049/JIMMUNOL.168.6.2603

关键词:

摘要: Mucosal mast cells strategically located at the optimal site interact with invading bacteria. Presence of VacA, virulent Helicobacter pylori cytotoxin, is correlated severity H. pylori-induced gastritis. To examine mechanisms inflammation in gastritis, we administered VacA to mice. Inoculation resulted epithelium vacuolization and marked infiltrations mononuclear into mucosal within 24 h. In an vitro study using bone marrow-derived cells, directly bound showed a chemotactic activity cell. addition, induced produce proinflammatory cytokines, TNF-α, macrophage-inflammatory protein-1α, IL-1β, IL-6, IL-10, IL-13 dose-dependent manner without causing degranulation. The present suggests that early activation by may be host response clear bacteria also contribute pathogenesis

参考文章(23)
Iwao Kurose, D.Neil Granger, Doyle J. Evans, Dolores G. Evans, David Y. Graham, Masayuki Miyasaka, D.C. Anderson, Robert E. Wolf, Gediminas Cepinskas, Peter R. Kvietys, Helicobacter pylori-induced microvascular protein leakage in rats: role of neutrophils, mast cells, and platelets. Gastroenterology. ,vol. 107, pp. 70- 79 ,(1994) , 10.1016/0016-5085(94)90062-0
T.L. Cover, M.J. Blaser, Purification and characterization of the vacuolating toxin from Helicobacter pylori. Journal of Biological Chemistry. ,vol. 267, pp. 10570- 10575 ,(1992) , 10.1016/S0021-9258(19)50054-0
D Taub, J Dastych, J Oppenheim, D Metcalfe, N Inamura, J Upton, D Kelvin, Bone marrow-derived murine mast cells migrate, but do not degranulate, in response to chemokines. Journal of Immunology. ,vol. 154, pp. 2393- 2402 ,(1995)
John C. Atherton, Ping Cao, Richard M. Peek, Murali K. R. Tummuru, Martin J. Blaser, Timothy L. Cover, Mosaicism in Vacuolating Cytotoxin Alleles of Helicobacter pylori ASSOCIATION OF SPECIFIC vacA TYPES WITH CYTOTOXIN PRODUCTION AND PEPTIC ULCERATION Journal of Biological Chemistry. ,vol. 270, pp. 17771- 17777 ,(1995) , 10.1074/JBC.270.30.17771
Kinnosuke Yahiro, Takuro Niidome, Miyuki Kimura, Tomomitsu Hatakeyama, Haruhiko Aoyagi, Hisao Kurazono, Ken-ichi Imagawa, Akihiro Wada, Joel Moss, Toshiya Hirayama, Activation of Helicobacter pylori VacA Toxin by Alkaline or Acid Conditions Increases Its Binding to a 250-kDa Receptor Protein-tyrosine Phosphatase β Journal of Biological Chemistry. ,vol. 274, pp. 36693- 36699 ,(1999) , 10.1074/JBC.274.51.36693
M. Marchetti, B. Arico, D. Burroni, N. Figura, R. Rappuoli, P. Ghiara, Development of a mouse model of Helicobacter pylori infection that mimics human disease. Science. ,vol. 267, pp. 1655- 1658 ,(1995) , 10.1126/SCIENCE.7886456
Kinnosuke Yahiro, Takuro Niidome, Tomomitsu Hatakeyama, Haruhiko Aoyagi, Hisao Kurazono, Philip Ian Padilla, Akihiro Wada, Toshiya Hirayama, Helicobacter pyloriVacuolating Cytotoxin Binds to the 140-kDa Protein in Human Gastric Cancer Cell Lines, AZ-521 and AGS Biochemical and Biophysical Research Communications. ,vol. 238, pp. 629- 632 ,(1997) , 10.1006/BBRC.1997.7345
J Yamamoto, C Ra, M Hirose, T Osada, N Sato, S Watanabe, Role of mast cells as a trigger of inflammation in Helicobacter pylori infection. Journal of Physiology and Pharmacology. ,vol. 50, pp. 17- 23 ,(1999)
VAN DOORN, VAN REES, NAMAVAR, GHIARA, VANDENBROUCKE-GRAULS, DE GRAAFF, The inflammatory response in CD1 mice shortly after infection with a CagA+/VacA+ Helicobacter pylori strain. Clinical and Experimental Immunology. ,vol. 115, pp. 421- 427 ,(1999) , 10.1046/J.1365-2249.1999.00789.X