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Infect. Immun. doi:10.1128/IAI.01459-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Candidatus Helicobacter heilmannii from Cynomolgus Monkey Brought about Gastric Low Grade MALT Lymphoma in C57BL/6 Mice

Masahiko Nakamura*, Somay Yamagata Murayama, Hiroshi Serizawa, Yukie Sekiya, Masahiro Eguchi, Shinichi Takahashi, Kaori Nishikawa, Tetsufumi Takahashi, Tsukasa Matsumoto, Haruki Yamada, Toshifumi Hibi, Kanji Tsuchimoto, and Hidenori Matsui

Center for Clinical Pharmacy and Clinical Sciences, School of Pharmaceutical Sciences, and Kitasato Institute for Life Sciences & Graduate School of Infection Control Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan, Center for Basic Research and Department of Internal Medicine, Kitasato Institute Hospital, The Kitasato Institute, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8642, Japan, 3rd Department of Internal Medicine, Kyorin University, Mitaka, Tokyo 181-8611, Japan, Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan

* To whom correspondence should be addressed. Email: nakamuram{at}pharm.kitasato-u.ac.jp.


   Abstract

Both Helicobacter pylori and Candidatus Helicobacter heilmannii infections are associated with peptic ulcers, gastric adenocarcinoma and gastric MALT lymphomas. However, good animal models of H. pylori clinical diseases are rare.

In this paper, we aim to establish an animal model of Candidatus Helicobacter heilmannii gastric MALT lymphoma. We used a urease-positive gastric mucosal and mucus homogenate of a cynomolgus monkey and maintained in C57BL/6 mouse stomachs. The contained bacterium was identified as Candidatus Helicobacter heilmannii based on DNA sequence analysis of the 16S rRNA and urease genes. Mucosal and mucus homogenates were used to inoculate C57BL/6 mice that were then examined over 24 months. We observed a gradual increase in the surface area of protrusive lesions in almost all infected C57BL/6 mice fundic stomachs at six months after infection. Light microscopic observations revealed an accumulation of B-lymphocytes with destruction of glandular elements and the presence of lymphoepithelial lesions consistent with low grade MALT lymphomas. Electron microscopic observation revealed numerous Candidatus Helicobacter heilmannii bacilli in the fundic glandular lumen, the intracellular canaliculi, and the cytoplasm of intact as well as damaged parietal cells. In conclusion, Candidatus Helicobacter heilmannii induced gastric MALT lymphoma in almost 100 percent of infected C57BL/6 mice after a period of six months associated with the destruction of parietal cells.




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