| Project/Area Number |
08044250
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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 Institution | Research Center for Advanced Sclence and Technology University of Tokyo |
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Principal Investigator |
KODAMA Tatsuhiko Research Canter for Advanced Sclence 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) |
ABURATANI Hiroyuki University Tokyo, Assistant Professor, 医学部・第三内科, 助手 (10202657)
EMI Mitsuru Nippon Medical Shool, Chalr Professor, 教授 (90221118)
NIKI Etsuo Research Center for Advanced Sclence and Technology University of Tokyo Chair Pr, 先端科学技術研究センター, 教授 (20011033)
DOI Takefumi Universversity of Osaka, Associae Professor, 薬学部・薬化学教室, 助教授 (00211409)
MINNICH Anne RhoneーPoulenc Rorer, 主任研究員
TRIGGVASON K カロリンスカ研究所, 生化学, 教授
YLAーHERTTUAL セッポ クオピオ大学, 分子生物学, 教授
FREEMAN Maso ハーバード大学, マサチューセッツ総合病院, 助教授
MAEDA Nobuyo ノースカロライナ大学, 病理学, 教授
GORDON Siamo オックスフォード大学, 病理学, 教授
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| Project Period (FY) |
1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 1996: ¥5,400,000 (Direct Cost: ¥5,400,000)
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| Keywords | Macrophage / Scavenger receptor / Lipoprotein / Atherosclerosis / Cholestrol / Cell Adhesion |
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| Research Abstract |
Type I and type II class A macrophage scavenger receptors (MSR-A) are implicated in the pathologic deposition of cholesterol during atherogenesis through receptor mediated uptake of modified low density lipoproteins (mLDL). MSR-A has an extraordinarily wide range of ligand binding capability including the bacterial pathogens, and is also known to mediate cation-independent macrophage adhesion in vitro. Here we report that the targeted disruption of the MSR-A gene results in a reduction in the size of atherosclerotic lesions in an apolipoprotein E (apo E) deficient animal. Macrophages from MSR-A deficient mice exhibit a marked decrease in mLDL uptake in vitro, whereas mLDL clearance from plasma occurs at a normal rate, suggesting that there are alternative mechanisms for the uptake of mLDL from the circulation. In addition, MSR-A knockout mice show increased susceptibility to Listeria monocytogenes infection and herpes simplex virus type-1 (HSV-1) infection, indicating a role for MSR-A in host defense against various pathogens.
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