Molecular mechanisms of the carbohydrate-dependent recognition and clearance of apoptotic cells and oxidized cells by macrophages.
| Project/Area Number |
13470492
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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 |
Biological pharmacy
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| Research Institution | Tokyo University of Pharmacy and Life Science |
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Principal Investigator |
BEPPU Masatoshi Tokyo University of Pharmacy and Life Science, School of Pharmacy, Professor, 薬学部, 教授 (60114633)
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| Co-Investigator(Kenkyū-buntansha) |
HIRANO Kazuya Tokyo University of Pharmacy and Life Science, School of Pharmacy, Assistant professor, 薬学部, 講師 (80251221)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥16,300,000 (Direct Cost: ¥16,300,000)
Fiscal Year 2003: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2002: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 2001: ¥8,100,000 (Direct Cost: ¥8,100,000)
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| Keywords | Macrophage / Apoptosis / Oxidative stress / Cell recognition / Carbohydrate recognition / Phagocytosis / Host defense / CD43 / レクチン |
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| Research Abstract |
Molecular mechanisms of the carbohydrate-mediated recognition of apoptotic cells and oxidized cells by macrophages were investigated. The major findings are listed below.
1.On the cell membrane of T-lymphocytes undergoing apoptosis, CD43 transiently forms caps, and the cells become susceptible to macrophage recognition through the carbohydrate chains of the CD43 caps.
2.Phosphatidylserine (PS) exposure and the exposed PS-mediated macrophage recognition of the apoptotic cells were observed later than the CD43 capping stage.
3.The carbohydrate-mediated macrophage recognition of the early apoptotic cells were observed in both cell line and primary cell systems.
4.Because induction of CD43 capping without apoptosis resulted also in the carbohydrate-mediated recognition, CD43 capping was a critical event for the recognition.
5.The activity of the macrophage receptor for the carbohydrate-mediated recognition of oxidized and apoptotic cells appeared to be regulated by intracellular redox system and calcium signaling.
6.The macrophage receptor for the carbohydrate-mediated recognition of oxidized cells and apoptotic cells was identified to be a known protein p110 by the following works :
1)p110 was demonstrated to be expressed on the macrophage surface.
2)Anti p110 antibody inhibited the binding of apoptotic cells and macrophages.
3)A soluble recombinant protein of p110 inhibited the binding of apoptotic cells and macrophages, and oligosaccharides blocked its inhibitory activity.
4) Non-phagocytic cells expressing recombinant p110 on cell surface were able to recognize the early apoptotic cells, while the wild type cells were not.
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Report
(4 results)
Research Products
(12 results)
