• Zhenxing Chen, Chang Liu, Yu Jiang, Hanchi Liu, Lina Shao, Kaiyuan Zhang, Daye Cheng, Ying Zhou, and Wei Chong.
• Department of Emergency, First Hospital of China Medical University, Shenyang, Liaoning, China.
• Shock. 2020 Sep 1; 54 (3): 321-329.

BackgroundAccumulating studies in recent years have revealed that platelet activation is an important factor inducing neutrophil extracellular traps (NETs) formation in vivo, while the mechanism of this process is not fully elaborated, restricting its clinical use. Our previous study found that a histone deacetylase inhibitor (HDACi) could attenuate serum H3 elevation in septic mice, which was related to NETs formation, and others found HDAC6 to be involved in platelet activation, indicating that HDACis may attenuate platelet activation and result in reduced NETs formation.MethodsFreshly isolated human platelets were activated by TRAP-6 with or without a HDACi, and secretion of α-granules was evaluated by testing PF4 in the supernatant using ELISA. NETs were induced by coincubating neutrophils with preactivated platelets, quantified by fluorescent intensity of Sytox green, monitored by live-cell imaging, and qualitatively analyzed by immunofluorescence.Main ResultsAn in vitro bioreactive system to induce and monitor NETs formation using platelets and neutrophils was established. The PF4 elevation stimulated by TRAP-6 in the supernatant of platelets was attenuated by the HDACi, and NETs formation that was induced by coincubating neutrophils with the preactivated platelets was decreased in the presence of the HDACi.ConclusionThe HDACi attenuates NETs formation induced by activated platelets partially by modulating the secretion of platelets.

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