| Project/Area Number |
13671077
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Jichi Medical School |
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Principal Investigator |
SAKATA Yoichi Jichi Medical School, Cell and molecular medicine, Professor, 医学部, 教授 (40129028)
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| Co-Investigator(Kenkyū-buntansha) |
MADOIWA Seiji Jichi Medical School, Cell and molecular medicine, Instructor, 医学部, 講師 (70296119)
MIMURO Jun Jichi Medical School, Cell and molecular medicine, Instructor, 医学部, 講師 (10221607)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2001: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | Plasminogen activator inhibitor-1 / granulocyte-derived elastase / Plasmin / fibrin / plasminogen-deficient mice / フィブリン分解産物 / プラスミノゲン / 白血球エラスターゼ / フィブリノゲン分解産物 |
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| Research Abstract |
We have hypothesized that there might be a kind of cross-talk between plasminogen activator-plasmin dependent fibrinolytic system and granulocyte-derived elastase dependent one, according to the following observations : 1, congenital plasminogen-deficient patients have no intravascular thrombophilic episodes. The granulocyte-derived elastase level of these patients in plasma is 10-100 times higher than that of the normal. Moreover, infusion of purified plasminogen decreases the level to a normal range. 2, plasminogen activator-plasmin dependent fibrinolytic system is supposed to be shutdown by remarkable increase of plasminogen activator inhibitor-1 in patient with disseminated intravascular coagulation associated with severe sepsis. Using ELISA system employing a monoclonal antibody specific to the granulocyte-derived elastase-fragment D species of human fibrin, we found that the elastase fibrin-digests were mostly elevated in these patients.
To support this hypothesis, we used plasminogen-deficient mice (KO mice) with synthetic elastase inhibitor. After the age of 7 weeks, 19% of KO mice develop rectal prolapse due to intravascular thrombosis in microcirculation. Unexpectedly, administration of elastase inhibitor protected KO mice from rectal prolapse. In addition, the amount of leukocyte infiltration and a fibrin deposit in the lung after lipopolysacharride loading were also decreased by concomitant elastase inhibition. These results suggest a cross-talk between two systems is more complicated and much more needs to be learned about the role of elastase in relation to alternative fibrinolytic system.
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