| Project/Area Number |
18K16117
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 54010:Hematology and medical oncology-related
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| Research Institution | Yamaguchi University |
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Principal Investigator |
Motoki Yukari 山口大学, 大学院医学系研究科, 講師 (80724054)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 抗リン脂質抗体 / 酸化ストレス / 血栓症 / 抗リン脂質抗体症候群 / 血管内皮細胞 / 単核球 |
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| Outline of Final Research Achievements |
In this study, we examined the thrombogenic effects of antiphospholipid antibodies and oxidative stress. Antiphospholipid antibodies promoted tissue factor expression, production of inflammatory cytokines and chemokines, and reactive oxygen species in vascular endothelial cells and peripheral blood mononuclear cells (PBMC). This effect was more pronounced when endothelial cells and PBMC were co-cultured under condition that allowed them to touch each other. Antiphospholipid antibodies also promoted adhesion of monocytes and lymphocytes to endothelial cells and infiltration under endothelial cells. Oxidative stress did not affect the production of proinflammatory cytokines and chemokines induced by antiphospholipid antibodies, but boosted monocyte adhesion to endothelial cells and subendothelial infiltration promoted by antiphospholipid antibodies.
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| Academic Significance and Societal Importance of the Research Achievements |
抗リン脂質抗体症候群は動脈・静脈を問わず繰り返し血栓症を起こすが、その機序については不明な点も多い。本研究は抗リン脂質抗体の有する炎症促進作用や細胞の遊走促進作用を明らかにし、加えて、抗リン脂質抗体症候群患者の血中が高度な酸化ストレス状態にあることに着目して、酸化ストレスが抗リン脂質抗体の作用の一部を補助することにより、相乗的に血管内に易血栓性をもたらす可能性を見出した。本研究の成果は、抗リン脂質抗体症候群の病態解明の一助となり、血栓症発症リスクを低減する予防法の切り口となる可能性が期待される。
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