| Project/Area Number |
18390041
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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 |
Environmental pharmacy
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| Research Institution | The University of Tokyo |
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Principal Investigator |
HIGASHI Nobuaki The University of Tokyo, Graduate School of Pharmaceutical Sciences, Associate Professor (40302616)
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| Co-Investigator(Kenkyū-buntansha) |
IRIMURA Tatsuro The University of Tokyo, Graduate School of Pharmaceutical Sciences, Professor (80092146)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥17,120,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥2,220,000)
Fiscal Year 2007: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
Fiscal Year 2006: ¥7,500,000 (Direct Cost: ¥7,500,000)
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| Keywords | extracellular matrix / inflammation / radiation injury / heparanase / mast cells / heparin / granulocytes / glycosaminoglycan / 細胞外マトリックス |
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| Research Abstract |
Heparanase was originally identified as an endo-beta-glucuronidase which cleaves heparan sulfate proteoglycan, and the enzyme' s pathological roles were extensively investigated in the field of cancer biology. In the present study, we examined functional relevance of heparanase in the immune system and biological responses to chemical stimuli and irradiation. Heparanase is involved in degradation of the basement membranes by monocytes. Capping of the molecule on the cell surface and subsequent redistribution at the leading edge are responsible for the degradation. A series of anti-mouse heparanase monoclonal antibodies were established and used to examine the intracellular distribution of the enzyme. Heparanase accumulation in the granules was detected in skin mast cells and in neutrophils in the inflamed microvasculature. Involvement of heparanase in heparin processing and modulation of granular function was examined. When heparanase gene or recombinant proteins were incorporated into MST mastcytoma cells, active heparanase was localized to the granules. In these modified MST cells, granular heparin was cleaved into a smaller molecular size and activity of granular enzymes seemed to be modulated by the low-molecular-weight heparin. Heparanase-mediated cleavage of heparan sulfate and heparin is likely to regulate processes essential to the functions of cells in the immune system and there by greatly involved in biological responses to chemical stimuli and irradiation.
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