The formation and disordered degradation of neutrophil extracellular traps in necrotizing lesions of anti-neutrophil cytoplasmic antibody-associated vasculitis

• Masuda, Sakiko

• Nonokawa, Mayu

• Futamata, Emika

• Nishibata, Yuka

• Iwasaki, Sari

• Tsuji, Takahiro

• Hatanaka, Yutaka

• Nakazawa, Daigo

• Tanaka, Satoshi

• Tomaru, Utano

• Kawakami, Tamihiro

• Atsumi, Tatsuya

• Ishizu, Akihiro

Bibliographic Information

Other Title

• Formation and Disordered Degradation of Neutrophil Extracellular Traps in Necrotizing Lesions of Anti-Neutrophil Cytoplasmic Antibody–Associated Vasculitis

Abstract

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is characterized by the production of ANCAs and systemic necrotizing vasculitis in small vessels. Disordered regulation of neutrophil extracellular traps (NETs) is critically involved in the pathogenesis of AAV. NETs are web-like DNA decorated with antimicrobial proteins; they are extruded from activated neutrophils. The principal degradation factor of NETs in vivo is DNase I; however, NETs resistant to DNase I can persist in tissues and lead to the production of ANCAs. Deposition of NETs has been demonstrated in glomerular crescents and necrotizing vasculitis in AAV. Here, the amount of NETs in formalin-fixed, paraffin-embedded tissue sections were examined and the results for AAV were compared with the results for diseases that should be distinguished from AAV. NETs were more abundant in necrotizing vasculitis of AAV than in non-ANCA-associated vasculitis, or in granulomatous angiitis. Pulmonary granulomas in AAV and non-ANCA-associated diseases were further studied. The amount of NETs was significantly greater in necrotizing granulomas of AAV than in granulomas of sarcoidosis without necrosis. Although NETs were formed in necrotizing granulomas of tuberculosis equivalently to those formed in AAV, they were more susceptible to degradation by DNase I than were NETs in AAV. The formation and disordered degradation of NETs in necrotizing lesions are characteristics of AAV, and are possibly related to its pathogenesis.

Journal

• The American journal of pathology

  The American journal of pathology 189 (4), 839-846, 2019-04

  Elsevier

Keywords

• NETs
• ANCA
• AAV
• DNaseⅠ

Details

• CRID: 1050002213034675200
• NII Article ID: 120006820166
• NII Book ID: AA12024839
• DOI: 10.1016/j.ajpath.2019.01.007
• ISSN: 15252191
• ISSN: 00029440
• HANDLE: 2115/77200
• Web Site: https://api.elsevier.com/content/article/PII:S0002944018307715?httpAccept=text/xml
• Web Site: https://api.elsevier.com/content/article/PII:S0002944018307715?httpAccept=text/plain
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN