Involvement of NETosis on the diabetic ulcers and development of novel wound care

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K19710
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Surgery related to the biological and sensory functions and related fields
• Research Institution: Tohoku University
• Principal Investigator: Tachi Masahiro 東北大学, 医学系研究科, 教授 (50312004)
• Co-Investigator(Kenkyū-buntansha): 菅野 恵美 東北大学, 医学系研究科, 准教授 (10431595) ; 丹野 寛大 東北大学, 医学系研究科, 助教 (10755664) ; 高木 尚之 東北大学, 医学系研究科, 助教 (30569471)
• Co-Investigator(Renkei-kenkyūsha): KAWAKAMI kazuyoshi 東北大学, 大学院医学系研究科, 教授 (10253973)
• Project Period (FY): 2017-06-30 – 2019-03-31
• Keywords: 創傷治癒 / 好中球 / NETosis（ネトーシス） / 好中球エラスターゼ

Outline of Final Research Achievements

It is well known about immunocompromised state and neutrophil dysfunction in diabetic foot ulcers. But the detailed mechanism of neutrophil dysfunction remains unclear.
In the current study, to identify the possible contribution of NETosis the co-localization between Ly6G (marker of neutrophils) and citrullinated histon (an indicator of NETosis) and elastase activity after α-mannan administration were examined. We discovered that the expression of citrullinated histone was accerated at the wound sites. In addition, elastase activity level was significantly higher in α-mannan-administrated mice than in vehicle-administered mice. We next investigated the effect of sivelestat sodium, a neutrophil elastase inhibitor, on wound closure in WT mice administered α-mannan, and the administration of sivelestat sodium was found to significantly improve the delayed wound closure caused by α-mannan.

Free Research Field

形成外科学

Academic Significance and Societal Importance of the Research Achievements

現在、慢性創傷における炎症遷延に対する治療法としては、抗菌薬などを用いた病原微生物に対する治療法が主流となっており、好中球など宿主因子に対する治療法は存在しない。
本研究により、宿主内の好中球がNETosis形成やエラスターゼが創傷治癒阻害要因としてクローズアップされ、今後、新規の治療ターゲットになる可能性が高い。