| Project/Area Number |
14570463
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Kansai Medical University (2003)
Kyoto University (2002) |
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Principal Investigator |
OKAZAKI Kazuichi Kansai Medical University, Faculty of Medicine, Professor, 医学部, 教授 (70145126)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Shin Kansai Medical University, Faculty of Medicine, Assistant Professor, 医学部, 講師 (40330211)
NAKANO Toshinari Kansai Medical University, Faculty of Medicine, Assistant Professor, 医学部, 講師 (60237344)
千葉 勉 京都大学, 医学研究科, 教授 (30188487)
八隅 秀二郎 京都大学, 医学研究科, 助手 (60332722)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Helicobacter pylori / MALT lymphoma / Th1 / Th1 immunity / dendritic cell |
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| Research Abstract |
In the present study, we developed gastric MALT lymphoma-like lesions in nTx mice by long-term H. pylori infection, and performed immunogenetic analyses. BALB/c mice were thymectomized on the 3rd day after birth. Follicle formation occurred after 2 months of H.pylori infection in the nTx mice. Follicle formation and infiltration of intraepithelial lymphocytes progressed in a time -dependent manner. Lymphoepithelial lesions, a characteristic feature of MALT lymphoma, also occurred in a time-dependent manner(100% at 12 months). Serum immunoelectrophoresis revealed a monoclonal band(M-protein) in 30%(3/10) of mice 6 months after infection. M-protein-positive mice had amplification of one or two IgM and/or IgG heavy-chain genes in the gastric B lymphocytes, as determined with polymerase chain reaction, suggesting mono-or oligoclonality. Overexpression of Bcl-X(L) protein was immunohistologically observed in the infiltrating B lymphocytes and in some follicular B lymphocytes in 80%(8/10) of
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the cases at 12 months. We also investigated the distribution of DC subsets using this model and examined their roles. To identify lymphoid and myeloid DCs, sections were stained with anti-CD11c(pan-DC marker) in combination with anti-CD8alpha(lymphoid DC marker) or anti-CD11ib(myeloid DC marker) and were examined with a con focal microscope. Expression of macrophage inflammatory protein 3alpha(MIP-3alpha), which chemoattracts immature DCs, was analyzed by real-time PCR and immunohistochemistry. Follicular dendritic cells(FDCs) were stained with anti-SKY28 antibodies. In noninfected nTx mice, a few myeloid and lymphoid DCs were observed in the bottom portion of the lamina propria, whereas in H. pylori-infected nTx mice, there was an increased influx of myeloid DCs throughout the lamina propria. FDC staining was also observed in the stomachs of members of the infected group. MIP-3alpha gene expression was upregulated in the infected nTx group, and the immunohistochemistry analysis revealed MIP-3alpha-positive epithelial cells. These data suggest that H. pylori infection upregulates MIP-3alpha gene expression in gastric epithelial cells and induces an influx of myeloid DCs in the lamina propria of the gastric mucosa in nTx mice. Myeloid DCs and FDCs might contribute to the development of gastric secondary lymphoid follicles in H. pylori-infected nTx mice. Most gastric mucosa-associated lymphoid tissue(MALT) lymphomas are caused by Helicobacter pylori(H.pylori) infection. Less
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