Title: | The formation and disordered degradation of neutrophil extracellular traps in necrotizing lesions of anti-neutrophil cytoplasmic antibody-associated vasculitis |
Authors: | Masuda, Sakiko Browse this author |
Nonokawa, Mayu Browse this author |
Futamata, Emika Browse this author |
Nishibata, Yuka Browse this author |
Iwasaki, Sari Browse this author →KAKEN DB |
Tsuji, Takahiro Browse this author |
Hatanaka, Yutaka Browse this author →KAKEN DB |
Nakazawa, Daigo Browse this author |
Tanaka, Satoshi Browse this author |
Tomaru, Utano Browse this author →KAKEN DB |
Kawakami, Tamihiro Browse this author |
Atsumi, Tatsuya Browse this author →KAKEN DB |
Ishizu, Akihiro Browse this author →KAKEN DB |
Keywords: | NETs |
ANCA |
AAV |
DNaseⅠ |
Issue Date: | Apr-2019 |
Publisher: | Elsevier |
Journal Title: | The American journal of pathology |
Volume: | 189 |
Issue: | 4 |
Start Page: | 839 |
End Page: | 846 |
Publisher DOI: | 10.1016/j.ajpath.2019.01.007 |
PMID: | 30677396 |
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. |
Rights: | © 2019, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
http://creativecommons.org/licenses/by-nc-nd/4.0/ |
Type: | article (author version) |
URI: | http://hdl.handle.net/2115/77200 |
Appears in Collections: | 保健科学院・保健科学研究院 (Graduate School of Health Sciences / Faculty of Health Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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