Molecular analyzes of sensitization phase of contact hypersensitivity
| Project/Area Number |
13672273
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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 |
Biological pharmacy
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| Research Institution | The University of Tokyo |
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Principal Investigator |
HIGASHI Nobuaki Graduate School of Pharmaceutical Sciences, The University of Tokyo, Lecturer, 大学院・薬学系研究科, 講師 (40302616)
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| Co-Investigator(Kenkyū-buntansha) |
IRIMURA Tatsuro Graduate School of Pharmaceutical Sciences, The University of Tokyo, Professor, 大学院・薬学系研究科, 教授 (80092146)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2002: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | macrophage / antigen presentation / lymph node / contact hypersensitivity / sialoadhesin / lectin / cell trafficking / dendritic cells / 糖鎖 / 感作 / COX-2 |
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| Research Abstract |
The aim of this proposal was to elucidate molecular mechanisms of sensitization phase of contact sensitivity, especially focusing on the entry of dermal macrophages to the draining lymph node and on the biological function of the cells inside the lymph node during the sensitization phase.
(1) Entry of dermal macrophages to the draining lymph node : Involvement of lectin-carbohydrate interaction in the entry of macrophages expressing macrophage galactose-type C-type lectin (MGL1) in the sensitization phase was investigated. Immunohistochemical localization of binding sites of recombinant MGL1 in LNs was revealed to be similar to distribution of cells expressing MGL1 apparently migrated from the dermis during sensitization. Affinity chromatography with immobilized recombinant MGL1 successfully purified a predominant component that was identified as sialoadhesin. Immobilize sialoadhesin actually bound recombinant MGL1 as well as MGL1-transfected CHO cells. The binding was dependent on the carbohydrates expressed on sialoadhesin. Immunohistochemical localization of sialoadhesin and MGL1 ligand coincided. Furthermore, sialoadhesin and MGL1 closely distributed in subcapsular sinus.
(2) Biological function of the dermal macrophages inside the lymph node during the sensitization phase : The aim of the study is to investigate how the MGL1 + cells modulate the sensitization phase. MGL+ cells were tested for the expression of cyclooxygenase (COXJ-2 mRNA. The cells expressed COX-2 mRNA and released PGE2, a final product of the COX-2-dependent prostanoids. The administration of a COX-2 inhibitor NS-398 during the sensitization phase inhibited the production of PGE2 in the lymph node and also antigen-dependent ear swelling of the sensitizad mice.
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Report
(3 results)
Research Products
(21 results)
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[Publications] Higashi N., Fujioka K., Denda-Nagai K., Hashimoto S., Nagai S., Sato T., Fujita Y, Morikawa A., Tsuiji M., Miyata-Takeuchi M., Sano Y, Suzuki N., Yamamoto K., Matsushima K., Irimura T.: "The macrophage C-type lectin specific for galactose/N-acetylgalactosamine is an endocytic receptor expressed on monocyte-derived immature dendritic ceils"J. Biol. Chem. 277. 20686-20693 (2002)
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