| Project/Area Number |
21K08665
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 55010:General surgery and pediatric surgery-related
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| Research Institution | Osaka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
前田 晃 大阪大学, 大学院医学系研究科, 招へい教員 (00319708)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | Xenotransplantation / 糖鎖認識部位 / SP-A / ブタ血管内皮細胞 / 細胞障害率 / Galectin 3/9 / 自然免疫系細胞 / 膜型レクチン / 異種移植 / Transgenicブタ / バイオ人工臓器 |
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| Outline of Research at the Start |
ヒトGalectin-3、-9及び 肺胞サーファクタントSP-AのCDR（糖鎖認識部位）部分を膜型レクチンの一つCL-1のCDRに置き換え、ブタ血管内皮細胞(SEC)に遺伝子発現させることにより、主にブタ細胞上でのMonocyte/Macrophageの制御、MonocyteのM2-Macrophageへ分化誘導、及び免疫寛容誘導の可能性、同時に好中球に対する反応を検討する。なお、比較に、ヒト組織適合性抗原のclass IbであるHLA-G群を用いる。
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| Outline of Final Research Achievements |
The present study aimed to examine the suppressive effect of surfactant protein A (SPA) on macrophage-mediated xenogeneic rejection. To investigate the effect of SPA on cytotoxicity and phagocytosis, THP-1 and human macrophages were co-cultured with SEC or SEC/SP-A, and the extent of phagocytosis and production of ROS were assessed. The mRNA expression levels of inflammatory cytokines in macrophages were determined using rt-PCR. The cytotoxicity and phagocytosis of SEC/SP-A were significantly decreased compared with those of naive SEC. Furthermore, the co-culture of human macrophages with SEC/SP-A decreased reactive oxygen species production, and the mRNA expression levels of TNFα were decreased in macrophages, whereas those of IL-10 were increased. In addition, NF-κB transcription was decreased in SEC/SP-A compared with that in SEC. In conclusion, the expression of SP-A represents an attractive method for xenotransplantation.
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| Academic Significance and Societal Importance of the Research Achievements |
この研究で、異種移植におけるmacrophageの働きを制御する分子が、一般にしられているCD47や、我々が初めて報告したCD200、TIGIT(T cell immunoreceptor with Ig and ITIM domains) 以外にも見つかった事で、macrophageに対する多角的な制御が可能になる事が判明した。今後、この自然免疫系細胞に対する研究を中心に異種移植全体の研究が進み、この分野の医療に大いなる進歩に繋がると考えられる。
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