| Project/Area Number |
08457033
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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 |
General medical chemistry
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| Research Institution | University of Tokyo |
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Principal Investigator |
SHIMIZU Takao The University of Tokyo, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (80127092)
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| Co-Investigator(Kenkyū-buntansha) |
KUME Kazuhiko The University of Tokyo, Graduate School of Medicine, Assistant Professor, 大学院・医学系研究科, 助手 (30251218)
IZUMI Takashi The University of Tokyo, Graduate School of Medicine, Assistant Professor, 大学院・医学系研究科, 助手 (70232361)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥7,400,000 (Direct Cost: ¥7,400,000)
Fiscal Year 1997: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1996: ¥4,600,000 (Direct Cost: ¥4,600,000)
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| Keywords | PAF / Platelet activating factor / homologous recombination / endotoxin / brain development / anaphylaxis / アレルギー / 標的遺伝子組み換え |
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| Research Abstract |
Platelet-activating factor (PAF) is a potent phospholipid mediator involved in inflammatory and allergic responses. It is also reported that PAF plays major roles in endotoxin-induced lethality, reproduction and brain development. To determine the role of PAF and its receptor in vivo, we generated a PAF receptor-deficient mice, by honologous recombination. Offspring were obtained with a Menderian distribution. They grow up normally, and no developmental changes are observed in any organs examined. The level of blood immunoglobulins and differential cell counts show no abnormality.
When the mice were sensitized and challenged with ovalbumin, the wild type mice showed a marked bronchial constriction, pulmonary edema, hypotension and death. On the other hand, the PAF receptor-deficient mice showed only moderate response to these treatments. Upon challenging with endotoxin, no significant difference was observed in both groups. Thus, we concluded that PAF is deeply involved in anaphylactic responses, while it shows minor role in the endotoxin-induced pathologies and lethality. Considering PAF antagonists show some protective effects on endotoxin-shock, even in PAF receptor knock-out mice, there may exist other targets of PAF receptor antagonists to protect the living system from endotoxin-induced disorders.
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