2005 Fiscal Year Final Research Report Summary
Chemical-induced hypersensitivity, cellular mechanism and its regulation
| Project/Area Number |
16390033
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Environmental pharmacy
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| Research Institution | The University of Tokyo |
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Principal Investigator |
NOBUAKI Higashi The University of Tokyo, Graduate School of Pharmaceutical Sciences, Associate Professor, 大学院・薬学系研究科, 助教授 (40302616)
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| Co-Investigator(Kenkyū-buntansha) |
TATSURO Irimura The University of Tokyo, Graduate School of Pharmaceutical Sciences, Professor, 大学院・薬学系研究科, 教授 (80092146)
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| Project Period (FY) |
2004 – 2005
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| Keywords | chemical-induced hypersensitivity / macrophages / dendritic cells / lymph nodes / lectin / skin inflammation / allergy / hapten |
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| Research Abstract |
Aim of the present research is to analyze cellular responses of mice that are treated with low molecular chemicals or haptens. We focus on cell surface antigens, cell behavior, migration, and physiological relevance of a subpopulation of skin macrophage/dendritic-lineage cells that are identified with cell surface expression of macrophage galactose-type C-type lectins 1/2 (MGL1/2).
Our main efforts are summarized on the following four points. (1)Migration of MGL1/2-positive cells from skin to draining lymph nodes was immunohistochemically confirmed. MGL1+MGL2+ cells in the lymph node were identified as dermal dendritic cells that carry hapten and are distinct from Langerhans cells. Another MGL+ cells (MGL1+MGL2-)were plasmacytoid dendtiric cells. (2)Sialoadhesin was identified as a counterreceptor of MGL1 that regulates migratory property of MGL1/2-positive cells from skin to draining lymph nodes. Another three candidates as MGL1- binding proteins were successfully detected and isolated in SDS-PAGE. (3)Crucial roles of MGL1 in contact hypersensitivity and antigen-induced granulation tissue formation were experimentally demonstrated using mouse disease models. During antigen-induced granulation tissue formation, the MGL1/2-positive cells produced inflammatory cytokines such as IL-1a and thus induced extracellular matrix synthesis in the tissue. (4)Mice deficient of MGL-1 expression or those injected with anti-MGL1 antibody (LOM-8.7)showed suppressed tissue formation during the antigen-dependent disease model. The effort (4)suggests that compounds that inhibit MGL-dependent binding are potentially utilized for anti-inflammatory drugs that can suppress migration or activation of MGL1/2-positive cells.
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