Investigation of Dysregulated Immunothrombosis in inflammatory diseases and development of a new therapeutic tool.
| Project/Area Number |
15K09459
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Keio University |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | ヒストン / 好中球 / 血小板 / Mac-1 / CD40L / PSGL-1 / 炎症 / 血栓 / 糖尿病 / Immunothrombosis |
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| Outline of Final Research Achievements |
Histones are released from damaged host cells and act as mediators of inflammation-related thrombosis. Platelet activation and aggregation is responsible for histone-induced thrombosis, but neutrophil-dependent mechanisms are still unclear. Immunodepletion of neutrophils and genetic ablation of Mac-1 protected mice from histone-induced pulmonary thromboembolism and prolonged survival. We utilized turbidimetric technic which estimates plasma clot production induced by interaction between human platelets and neutrophils in the presence of plasma in vitro. Histones augmented the plasma clot production in Mac-1-dependent manner and enhanced platelet-neutrophil complex formation which is inhibited by anti-Mac-1 antibody. Furthermore histones could directly activate Mac-1 besides through platelets . In conclusion, histones induces Mac-1-dependent thromboembolism through neutrophil-platelet interaction, which is a new therapeutic target for inflammation-induced thrombosis.
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Report
(4 results)
Research Products
(9 results)
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[Journal Article] Macrophage extracellular chromatin release induced by Mac-1 mediated platelet-macrophage interactions triggers acute kidney injury in rhabdomyolysis.2018
Author(s)
Okubo K, Kurosawa M, Kamiya M, Urano Y, Suzuki A, Yamamoto K, Hase K, Homma K, Sasaki J, Miyauchi H, Hoshino T, Hayashi M, Mayadas TN, Hirahashi J.
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Journal Title
Nat. Med.
Volume: 24
Issue: 2
Pages: 232-238
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Lactoferrin Suppresses Neutrophil Extracellular Traps Release in Inflammation.2016
Author(s)
Okubo K, Kamiya M, Urano Y, Nishi H, Herter JM, Mayadas T, Hirohama D, Suzuki K, Kawakami H, Tanaka M, Kurosawa M, Kagaya S, Hishikawa K, Nangaku M, Fujita T, Hayashi M, Hirahashi J.
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Journal Title
EBioMedicine
Volume: 10
Pages: 204-215
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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