Uric acid induces NADPH oxidase-independent neutrophil extracellular trap formation
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- 作者：Yasuyuki Arai ; Yoko Nishinaka ; Toshiyuki Arai ; Makiko Morita ; Kiyomi Mizugishi ; Souichi Adachi ; Akifumi Takaori-Kondo ; Tomohiro Watanabe ; Kouhei Yamashita
- 关键词：CGD ; chronic granulomatous disease ; DHR ; dihydrorhodamine 123 ; DPI ; diphenyleneiodonium ; HBSS ; Hanks&rsquo ; balanced salt solution ; MSU ; monosodium urate ; MVP ; trans-1-(2&prime ; -methoxyvinyl)pyrene ; Nox ; NADPH oxidase ; NET ; neutrophil extracellular trap ; PBN ; 伪-phenyl-N-tert-butyl nitrone ; PMA ; phorbol myristate acetate ; ROS ; reactive oxygen species ; 1O2 ; singlet oxygen ; UA ; uric acid
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：10 January, 2014
- 年：2014
- 卷：443
- 期：2
- 页码：556-561
- 全文大小：1860 K
文摘
Neutrophil extracellular traps (NETs) are composed of extracellular DNA fibers with antimicrobial peptides that capture and kill microbes. NETs play a critical role in innate host defense and in autoimmune and inflammatory diseases. While the mechanism of NET formation remains unclear, reactive oxygen species (ROS) produced via activation of NADPH oxidase (Nox) are known to be an important requirement. In this study, we investigated the effect of uric acid (UA) on NET formation. UA, a well-known ROS scavenger, was found to suppress Nox-dependent ROS release in a dose-dependent manner. Low concentrations of UA significantly inhibited Nox-dependent NET formation. However, high concentrations of UA unexpectedly induced, rather than inhibited, NET formation. NETs were directly induced by UA alone in a Nox-independent manner, as revealed by experiments using control neutrophils treated with ROS inhibitors or neutrophils of patients with chronic granulomatous disease who have a congenital defect in ROS production. Furthermore, we found that UA-induced NET formation was partially mediated by NF-魏B activation. Our study is the first to demonstrate the novel function of UA in NET formation and may provide insight into the management of patients with hyperuricemia.