2017 Fiscal Year Final Research Report
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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| Keywords | ヒストン / 好中球 / 血小板 / Mac-1 / CD40L / PSGL-1 |
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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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| Free Research Field |
炎症と血栓
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