| Project/Area Number |
09044261
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Field |
General medical chemistry
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| Research Institution | Research Center for Advanced Science and Technology University of Tokyo |
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Principal Investigator |
KODAMA Tatsuhiko Research Center for Advanced and Technology University of Tokyo, Chair Professor, 先端科学技術研究センター, 教授 (90170266)
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| Co-Investigator(Kenkyū-buntansha) |
DOI Takefumi University Of Osaka, Associate Professor, 薬学部, 助教授 (00211409)
MATOU Masao International University of Heslth and Welfare, Chair Professor, 保健学部, 教授 (80048941)
TRIGGVASON K カロリンスカ研究所生化学, 教授
MAEDA Nobuyo The University Of North Carolina At Chapel Hill Department of Phathology and Lab, 病理学, 教授
GORDON Siamon University Of Oxford Sir William Duun School Of Pathology, Chair Professor, 病理学, 教授
TRYGGVASON Karl Karolinska Institutet Department of Medical Biochemistry and Biophysics.Chair Pr
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| Project Period (FY) |
1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 1997: ¥6,600,000 (Direct Cost: ¥6,600,000)
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| Keywords | macrophage / scavenger receptor / knockout mice / foam cell / atherosclerosis / 脳虚血性疾患 / ミクログリア / 酸化LDL |
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| Research Abstract |
Macrophage type-I and type-II class-A scavenger receptors (MSR-A) are implicated in the pathological deposition of cholesterol during atherogenesis as a result of receptor-mediated uptake of modified low-density lipoproteins (mLDL). MSR-A can bind an extraordinarily wide range of ligands, including bacterial pathogens, and also mediates cation-independent marcrophage adhesion in vitro. Here we show that targeted disruption of the MSR-A gene in mice results in a reduction in the size of atherosclerotic lesions in an animal deficient in apolipoprotein E.Macrophages from MSR-A-dificient mice show a marked decrease in mLDL uptake in vitro, whereas mLDL clearance from plasma occurs at a normal rate, indicating that there may be alternative mechanisms for removing mLDL from the circulation. In addition, MSR-A-knockout mice show an increased susceptibility to infection with Listeria monocytogenes or herpes simplex virus type-1, indicating that MSR-A may play a part in host defense against pathogens.
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