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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.01252

PRAK is required for the formation of neutrophil extracellular traps

 Yan Wang1, Yuqing Wang1, Jia Wu1,  Chen Liu2, Yu Zhou3, Ligu Mi1, Yu Zhang1, 4* and  Wei Wang1*
  • 1Department of Immunology, School of Basic Medical Sciences, Peking University, China
  • 2Department of Clinical Laboratory, Cancer Hospital (CAMS), China
  • 3Peking Union Medical College Hospital (CAMS), China
  • 4Institute of Biological Sciences, Jinzhou Medical University, China

Neutrophil extracellular traps (NETs) are one of the most powerful and specific tools for neutrophils to clean up extracellular microbes, but the mechanisms of NETosis under infection are scarcely studied. In this study, by examining the neutrophils from human peripheral blood and mouse abdomen, we demonstrated that PRAK dysfunction resulted in a significantly reduced NET formation and elevated apoptotic cells. Furthermore, PRAK dysfunction could lead to impaired NET-mediated antibacterial activity and shorten the survival of mice with CLP-induced sepsis. Mechanism studies revealed that attenuated NET formation in PRAK dysfunctional neutrophils correlated with unregulated reactive oxygen species (ROS), which triggered apoptosis through excessive autophagy. The imbalance of NET formation and apoptosis was further regulated by treatment with lower ROS in hypoxia. Here, we propose a novel candidate, PRAK, which can sense the oxidative stress and regulate the releasing of ROS, may be the master molecular switch to regulate the NETosis-apoptosis axis of neutrophils.

Keywords: neutrophil extracellular traps (NETs), PRAK, reactive oxygen species (ROS), Autophagy, Apoptosis

Received: 09 Feb 2019; Accepted: 17 May 2019.

Edited by:

Cees Van Kooten, Leiden University, Netherlands

Reviewed by:

Yi Zhao, West China Hospital, Sichuan University, China
Carmelo Carmona-Rivera, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), United States
Federico Pratesi, University of Pisa, Italy
Meraj A. Khan, Hospital for Sick Children, Canada  

Copyright: © 2019 Wang, Wang, Wu, Liu, Zhou, Mi, Zhang and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Yu Zhang, Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, China, zhangyu007@bjmu.edu.cn
Prof. Wei Wang, Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, China, wangwei83427@bjmu.edu.cn