Effects of procoagulant vesicles shed from monocytic cells on adverse events following autologous blood transfusion

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K09234
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: National Center for Global Health and Medicine
• Principal Investigator: Azma Toshiharu 国立研究開発法人国立国際医療研究センター, その他部局等, 医師 (60284197)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 単球 / 組織因子 / アポトーシス / 凝固活性小胞

Outline of Final Research Achievements

The effects of rewarming after cold exposure on human monocytic cells (THP-1) were investigated. THP-1 cells were subjected to cold exposure at 4°C for pre-selected periods and then rewarmed to 37°C. After more than 8 hours of cold exposure and subsequent rewarming,apoptotic cells increased following the decrease in mitochondrial membrane potential in these cells. Calcium influx was suggested to be the main cause of apoptosis, as calcium chelators showed inhibitory effects, while reactive oxygen species were not involved. By contrast, tissue factor release was observed after cold exposure, which was suppressed by antioxidants. These findings suggest that different molecular mechanisms are involved in apoptosis induction and tissue factor release following cold exposure.

Free Research Field

Anesthesiology

Academic Significance and Societal Importance of the Research Achievements

低温曝露によるアポトーシス誘導には細胞外カルシウムの細胞内への流入が関与すると考えられたが，活性酸素種はTHP-1の低温曝露によるアポトーシス誘導に影響を与えなかった．一方，THP-1は低温曝露により組織因子を放出し，活性酸素種はこれを抑制した．血液製剤の保存溶液にはカルシウムキレート薬が含まれているが，活性酸素種の消去薬は含まれていない．今回の知見により，白血球を含む血液製剤を保存する溶液に活性酸素種を消去する作用をもつ薬剤を添加することで輸血に関連する血栓形成性を抑制制御可能であることが示唆された．