Utilization of regulatory functions of (membrane-type) lectins in bioartificial organ research

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08665
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Osaka University
• Principal Investigator: MASAHATA Kazunori 大阪大学, 大学院医学系研究科, 招へい教員 (40588381)
• 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)
• Project Period (FY): 2021-04-01 – 2024-03-31
• 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

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.

Free Research Field

Xenotransplantation

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。