| Project/Area Number |
12470079
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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 |
Immunology
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| Research Institution | Fukushima Medical University School of Medicine |
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Principal Investigator |
FUJITA Teizo Fukushima Medical University, School of Medicine, professor, 医学部, 教授 (20134223)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Minoru Fukushima Medical University, School of Medicine, assistant professor, 医学部, 助手 (00285024)
MATSUSHITA Misao Tokai University, Institute of Glycotechnology, professor, 工学部, 教授 (00165812)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥14,000,000 (Direct Cost: ¥14,000,000)
Fiscal Year 2002: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2001: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2000: ¥6,300,000 (Direct Cost: ¥6,300,000)
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| Keywords | Ficolin / Lectin / Host defeuse / complement / Lectin pathway / Gene targeting / MASP / 分子進化 / 自然免疫 / 遺伝子改変マウス |
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| Research Abstract |
Discrimination between self and non-self by lectins is a strategy of innate immunity that is found in both vertebrates and invertebrates. In vertebrates, immune recognition is mediated by ficolins as well as mannose-binding lectin (MBL). Ficolins are the proteins characterized by the presence of an N-terminal collagen-like domain and a C-terminal fibrinogen-like domain, and have been identified in mammalians such as pig, mouse and human. In this project, human L-and H-ficolins were found to form complexes with MASPs, Cis-like serine proteases and sMAP, a truncated form of MASP-2. Upon recognition of carbohydrate patterns on invading microorganisms by these ficolins, the associated MASPs were activated to cleave the complements C3/C4 through the lectin complement pathway. L-ficolin recognized lipteicholic acid and 1,3-β-D glucan, components in the cell wall of microorganisms, as well as N-acetylglucosamine residue on glycoproteins. To further clarify the physiological roles of ficolins and MASPs/sMAP we established ficolin A-deficient and Maspi-deficient mice using gene targeting technique. The phenotype of ficolin A-dificient mice is now under investigation. Masp-1 deficient mice were more susceptible for infection by influenza virus. Sera from Masp 1-deficient mice showed low activation of Masp-2 from the proenzyme form, followed by a delay of complement activation. To explore primitive system of the lectin pathway, ficolins and the other components of the lectin pathway were isolated from lower animals such as ascidian Halocynthia rorezti, our closest invertebrate relatives. The system was suggested to be simply consisted of three components, recognition molecules (ficolin-like and MBL-like lectins), MASP and complement C3. These results suggest that ficolins have a pivotal role as recognition molecules for host defense in all species which emerged after ascidians.
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