2022 Fiscal Year Final Research Report
Elucidation of thrombus formation by antiphospholipid antibody
Project/Area Number |
20K16547
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 52010:General internal medicine-related
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Research Institution | Yamaguchi University |
Principal Investigator |
Kaneshige Risa 山口大学, 大学院医学系研究科, 助教 (30844104)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | 抗リン脂質抗体症候群 / 抗リン脂質抗体 / CD14抗原 / 好中球細胞外トラップ |
Outline of Final Research Achievements |
The purpose of this study was to elucidate various thrombus formation and cytotoxic effects by antiphospholipid antibody (aPL). The results of this study indicate that inflammatory cytokines have a positive priming effect on aPL-induced monocyte surface tissue factor (TF) expression. Moreover, we revealed a signal by aPLs was transmitted via CD14 and may induce various inflammatory reactions such as TF expression on monocytes. Furthermore, we found that aPL induces the formation of neutrophil extracellular traps (NETs). In APS patients, it can be speculated that aPL amplifies the thrombogenic effect centered on NETs and monocyte surface TF expression. These findings have important potential not only to elucidate the pathogenesis of APS, but also to serve as evidence for new therapeutic strategies.
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Free Research Field |
血栓止血学 臨床検査医学
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Academic Significance and Societal Importance of the Research Achievements |
aPLにより引き起こされる、単球表面 TF 発現による外因系凝固の活性化や血管障害・血管炎症に関与するNETs形成促進作用は、APSにおける動・静脈血栓症発症機序の中心的な役割を担っていると推測される。 本研究において、aPL刺激による単球表面TF発現に関与している細胞表面レセプターを解明するとともに、TF発現が炎症性サイトカインにより増強されること、好中球が関与する血栓形成作用(NETs形成)についても明らかにした。本研究成果はAPSの病態発症機序の解明に繋がるのみならず、新たな治療戦略のエビデンスとなる可能性が期待される。
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