| Project/Area Number |
07044224
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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 | University of Tokyo |
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Principal Investigator |
KODAMA Tatsuhiko The Third Department of Internal Medicine School of Medicine, University of Tokyo, Assistant, 医学部(病), 助手 (90170266)
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| Co-Investigator(Kenkyū-buntansha) |
DOI Takefumi University of Osaka, 薬学部, 助教授 (00211409)
YLA-HERTTUALA Seppo Kuopin Univ., 医学部, 助教授
FREEMAN Mason W. Harvard Univ., 医学部, 教授
MAEDA Nobuyo North Carolina Univ., 医学部, 教授
GORDON Siamon Oxford Univ., 医学部, 教授
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| Project Period (FY) |
1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 1995: ¥5,800,000 (Direct Cost: ¥5,800,000)
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| Keywords | macrophage / atherosclerosis / scavenger receptor / cholesterol / Mato cell / foam cell / knockout mice / apo E knockout |
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| Research Abstract |
The role of macrophage scavenger receptors on atherogenesis was analyzed using scavenger receptor knockout mice. The scavenger receptor knockout mice was established in Tokyo University, and was analyzed pathologically in Oxford University using 2F8 monoclonal antibody. Macrophages deficient in scavenger receptor were less adhesive to plastic dishes after EDTA treatment. Phagocytic activity and endocytosis activity was lower in scavenger receptor deficient mice than in normal cntrol. The mean survival time after LPS treatment is short in scavenger receptor knockout mice.
Apo E deficient mice, which is a useful model for atherosclerosis analysis, was established in the North Carolina University. The mice was mated with scavenger receptor deficient mice. The double knockout mice developed smaller lesion than apo E single knockout mice. This result is the first evidence indicating that scavenger receptor is truely involved in the atherome formation in vivo.
Dr.Freeman in Harvard University analyzed the structure of scavenger receptor promoter. Analysis using the transgenic mice expressing X-Gal under scavenger receptor promoter indicated that scavenger receptor promoter can mediate macrophage specific gene expression, and also mediate the gene expression in atherome.
One of the most important progress is the further characterization of Mato's fluorescent granular perithelial cell in the brain cortex. Dr.Herttuala of Kuopio University indicated that in human brain cortex, only Mato cells expressed Scvaenger receptor mRNA.Dr.Gordon indicated that in mouse brain, only Mato cells expressed scavenger receptor protein. From these results we proposed Mato cell as brain scavenger cell which is involved in scavenger and barrier function in both human and animal brain cortex.
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