Zhenxing Chen1, Chang Liu1, Yu Jiang1, Hanchi Liu1, Lina Shao1, Kaiyuan Zhang2, Daye Cheng3, Ying Zhou4, Wei Chong1. 1. Department of Emergency, First Hospital of China Medical University, Shenyang, Liaoning, China. 2. Department of Laboratory Medicine, First Hospital of China Medical University, Shenyang, Liaoning, China. 3. Department of Transfusion, First Hospital of China Medical University, Shenyang, Liaoning, China. 4. Health Examination Center, First Hospital of China Medical University, Shenyang, Liaoning, China.
Abstract
BACKGROUND: Accumulating 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. METHODS: Freshly 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 RESULTS: An 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. CONCLUSION: The HDACi attenuates NETs formation induced by activated platelets partially by modulating the secretion of platelets.
BACKGROUND: Accumulating 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. METHODS: Freshly 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 RESULTS: An 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. CONCLUSION: The HDACi attenuates NETs formation induced by activated platelets partially by modulating the secretion of platelets.