2019 Fiscal Year Final Research Report
Study on prolonging survival of small intestine grafts by inhibiting macrophages
| Project/Area Number |
17K17001
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pediatric surgery
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| Research Institution | Hyogo Medical University (2019)
Osaka University (2017-2018) |
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Principal Investigator |
Kodama Tasuku 兵庫医科大学, 医学部, 病院助手 (60771045)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | 小腸移植 / マクロファージ / 免疫抑制 / ラット |
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| Outline of Final Research Achievements |
The effect of PQA-18, a novel immunosuppressive agent that inhibits PAK-2 and suppresses cytokine production and macrophage (Mφ) ifferentiation/proliferation, was evaluated using a rat small intestine transplant model.
Recipients were administered PQA-18 (4 mg/kg) intraperitoneal injection from post-operative day1 (POD1) to two weeks.The survival time of the graft was prolonged in the PQA administered group (PQA) than in the non-administration group (ITx). At POD6, suppression of recipient T cell proliferation, and suppression of Mφ infiltration into graft lymph nodes were observed in the PQA group.Further, when 20μM of PQA-18 was added to bone marrow stem cells and cultured, suppression of differentiation into Mφ was observed.
It was found that PQA-18 prolongs the survival of small intestine grafts and suppresses the infiltration of Mφ into the grafts and lymph nodes.
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| Free Research Field |
小児外科
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| Academic Significance and Societal Importance of the Research Achievements |
小腸移植後のグラフト生存期間は他の臓器と比較すると芳しくない。これは小腸自体が外界と接するためマクロファージといった自然免疫が発達していることと、既存の免疫抑制剤ではしばしば腎機能障害を認めることが原因として考えられる。
今回、ラット小腸移植後にマクロファージの増殖・分化を抑制する新規免疫抑制剤であるPQA-18を投与したところ、腎機能障害といった副作用なく、小腸移植グラフトの生存期間の延長を認め、グラフトリンパ節内のマクロファージ減少を認めた。今後、既存の免疫抑制剤と併用することで、副作用を軽減し小腸移植グラフトのさらなる生存期間延長が期待できる可能性が考慮された。
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