Elucidation of DNase resistance acquisition mechanism of neutrophil extracellular traps in ANCA-associated vasculitis

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16575
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Hokkaido University
• Principal Investigator: Masuda Sakiko 北海道大学, 保健科学研究院, 講師 (10763617)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: ANCA関連血管炎 / 好中球細胞外トラップ / NETs / DNase I

Outline of Final Research Achievements

The proteins of DNase I-sensitive NETs or DNase I-resistant NETs were compared by proteomics analysis, and narrowed down 18 protein candidates that are considered to confer DNase I resistance to NETs. When candidate proteins were added during NET induction, the formation of normal NET was suppressed by the five proteins, and the formation of abnormal NET resistant to DNase I became the main component. Addition of an inhibitory antibody to one of these proteins during NETs induction suppressed the formation of normal and abnormal NETs.

Free Research Field

実験病理学

Academic Significance and Societal Importance of the Research Achievements

ANCA関連血管炎では分解因子DNase Iに抵抗性を持つNETsが産生され、その結果自己抗体の産生や組織障害が誘導される。本研究では、NETsにDNase I抵抗性を付与する可能性のあるタンパクを絞り込んだ。そのうちの１つのタンパクに対する阻害抗体は異常なDNase I抵抗性NETsの産生を抑制したことから、本研究の成果はDNase I抵抗性NETsが関連する疾患の治療に応用できる可能性がある。