PRAK Is Required for the Formation of Neutrophil Extracellular Traps
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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.01252/full |
| _version_ | 1828412027603779584 |
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| author | Yan Wang Yuqing Wang Jia Wu Chen Liu Yu Zhou Ligu Mi Yu Zhang Yu Zhang Wei Wang |
| author_facet | Yan Wang Yuqing Wang Jia Wu Chen Liu Yu Zhou Ligu Mi Yu Zhang Yu Zhang Wei Wang |
| author_sort | Yan Wang |
| collection | DOAJ |
| description | 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 overproduction of 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. |
| first_indexed | 2024-12-10T12:41:50Z |
| format | Article |
| id | doaj.art-eefe75c2181f40a18b87a336eb3fa388 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T12:41:50Z |
| publishDate | 2019-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-eefe75c2181f40a18b87a336eb3fa3882022-12-22T01:48:31ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-06-011010.3389/fimmu.2019.01252446422PRAK Is Required for the Formation of Neutrophil Extracellular TrapsYan Wang0Yuqing Wang1Jia Wu2Chen Liu3Yu Zhou4Ligu Mi5Yu Zhang6Yu Zhang7Wei Wang8Department of Immunology, School of Basic Medical Sciences, NHC Key Laboratory of Medical Immunology, Peking University, Beijing, ChinaDepartment of Immunology, School of Basic Medical Sciences, NHC Key Laboratory of Medical Immunology, Peking University, Beijing, ChinaDepartment of Immunology, School of Basic Medical Sciences, NHC Key Laboratory of Medical Immunology, Peking University, Beijing, ChinaDepartment of Clinical Laboratory, Peking University People's Hospital, Beijing, ChinaDepartment of Pharmacology, Institute of Materia Medica, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaDepartment of Immunology, School of Basic Medical Sciences, NHC Key Laboratory of Medical Immunology, Peking University, Beijing, ChinaDepartment of Immunology, School of Basic Medical Sciences, NHC Key Laboratory of Medical Immunology, Peking University, Beijing, ChinaInstitute of Biological Sciences, Jinzhou Medical University, Jinzhou, ChinaDepartment of Immunology, School of Basic Medical Sciences, NHC Key Laboratory of Medical Immunology, Peking University, Beijing, ChinaNeutrophil 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 overproduction of 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.https://www.frontiersin.org/article/10.3389/fimmu.2019.01252/fullneutrophil extracellular traps (NETs)PRAKreactive oxygen species (ROS)autophagyapoptosis |
| spellingShingle | Yan Wang Yuqing Wang Jia Wu Chen Liu Yu Zhou Ligu Mi Yu Zhang Yu Zhang Wei Wang PRAK Is Required for the Formation of Neutrophil Extracellular Traps Frontiers in Immunology neutrophil extracellular traps (NETs) PRAK reactive oxygen species (ROS) autophagy apoptosis |
| title | PRAK Is Required for the Formation of Neutrophil Extracellular Traps |
| title_full | PRAK Is Required for the Formation of Neutrophil Extracellular Traps |
| title_fullStr | PRAK Is Required for the Formation of Neutrophil Extracellular Traps |
| title_full_unstemmed | PRAK Is Required for the Formation of Neutrophil Extracellular Traps |
| title_short | PRAK Is Required for the Formation of Neutrophil Extracellular Traps |
| title_sort | prak is required for the formation of neutrophil extracellular traps |
| topic | neutrophil extracellular traps (NETs) PRAK reactive oxygen species (ROS) autophagy apoptosis |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.01252/full |
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