Development of early diagnosis of thrombosis induced by neutrophil extracellular traps

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07432
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Himeji Dokkyo University
• Principal Investigator: Tohyama Yumi 姫路獨協大学, 薬学部, 教授 (70362770)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 好中球 / NETs

Outline of Final Research Achievements

Neutrophil extracellular traps (NETs) formation is a biological defense mechanism in which neutrophil chromatin changes into a meshwork to capture pathogenic microorganisms. In this study, we focused on the fact that NETs stimulate platelets to induce thrombosis, and aimed to elucidate the mechanism of NETs formation and to identify the NETs components that activate platelets.
Using a knockout neutrophil model, we analyzed the intracellular chemical reactions that occur during NETs formation and found that regulation of the neutrophil cytoskeleton is essential for NETs formation. Furthermore, we are investigating two proteins that are abundant in neutrophils as candidate molecules for NETs-derived platelet activation.

Free Research Field

生化学、免疫学

Academic Significance and Societal Importance of the Research Achievements

Neutrophil extracellular traps(NETs)は、好中球のクロマチンが網状構造に変化して病原微生物を捉える生体防御機構であるが、近年、NETs成分が血小板を刺激して血栓症を誘発することが新たな病態として注目されている。
そこで本研究では、NETs形成の分子メカニズムと、NETsが血小板の活性化を介して血栓症に至るプロセスの解明に取り組んだ。研究成果の学術的意義として、好中球の細胞骨格の制御が、NETs形成に必須であることを見いだした。さらに社会的意義として、NETs由来の２種類のタンパク質を血小板活性化候補として提案した。血栓症の早期診断法の開発に寄与する。