| 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)
|
|---|
| 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.
|
