| Project/Area Number |
08457071
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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 |
Experimental pathology
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| Research Institution | Kumamoto University |
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Principal Investigator |
TAKAHASHI Kiyoshi SCHOOL OF MEDICINE,PROF., 医学部, 教授 (70045631)
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| Co-Investigator(Kenkyū-buntansha) |
KODAMA Tatsuhiko UNIVERSITY OF TOKYO・RESEARCH CENTER FOR ADVANCED SCIENCE AND TECHNOLOGY,PROF., 先端科学技術研究センター, 教授 (90170266)
MIYAKAWA Kazuhisa SCHOOL OF MEDICINE,ASSISTANT, 医学部, 助手 (00244111)
TAKEYA Motohiro SCHOOL OF MEDICINE,ASSOC.PROF., 医学部, 助教授 (90155052)
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥7,100,000 (Direct Cost: ¥7,100,000)
Fiscal Year 1998: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1997: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1996: ¥3,900,000 (Direct Cost: ¥3,900,000)
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| Keywords | scavenger receptors / macrophages / atherosclerosis / foam cells / gene targeted mice / granuloma / immunohistochemistry / monoclonal antibodies / 免疫組織科学 / ヒトMSR / 動脈硬化症 / 免疫電顕 / AGE / MSR knock out mouse / 修飾LDL / 細胞内動態 |
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| Research Abstract |
1. Anti-human monoclonal antibodies for macrophage scavenger receptors (MSR), as well as polyclonal antibodies for synthetic peptides of MSR, were generated in our laboratory. Using these antibodies, our immunohistochemical and immunoelectron microscopic studies demonstrated that MSR was distributed on the cell membranes of macrophages ubiquitously distributed in various organs and tissues of humans. Immunohistochemical and immunoelectron microscopic investigation with anti-bovine or anti-murine MSR monoclonal antibodies revealed similar distribution and subcellar localization of MSR in bovine and murine tissues.
2. Our studies demonstrated in humans, bovines, and mice that MSR can bind to modified low density lipoproteins (LDL) such as acetylated LDL (acLDL) or oxidized LDL (oxLDL) and to advanced glycation end products (AGE). MSR-deficient mice revealed marked reductions in the uptake of acLDL, oxLDL, and AGE.
3. In atheroselerotic lesions of human aorta, macrophage-derived foam cells showed the expression of MSR and intracellular accumulation of oxLDL and AGE.In apo-E/MSR double knockout mice and diet-induced LDL receptor/MSR double knockout mice, the lesion size of atheroselerosis was markedly reduced in the aorta, compared with apo-E or diet-induced LDL receptor-single knockout mice, indicating that MSR is deeply implicated in atherognesis.
4. Compared with the wild-type mice, the hepatic granuloma formation induced by intravenous injection of heat-killed Corynebacterium parvum (C.parvum) was delayed and the uptake of C.parvum by Kupffer cells was markedly impaire in MSR-deficient mice, particularly in the early stage. These results indicate that MSR is involved in the defense mechanisms against exogenously invading bacteria.
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