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Publication : PRAK Is Required for the Formation of Neutrophil Extracellular Traps.

First Author  Wang Y Year  2019
Journal  Front Immunol Volume  10
Pages  1252 PubMed ID  31231384
Mgi Jnum  J:287880 Mgi Id  MGI:6415920
Doi  10.3389/fimmu.2019.01252 Citation  Wang Y, et al. (2019) PRAK Is Required for the Formation of Neutrophil Extracellular Traps. Front Immunol 10:1252
abstractText  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.
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