HMGB1-activatied NLRP3 inflammasome induces thrombocytopenia in heatstroke rat

PeerJ

article

Huimei Yin¹  Ming Wu²  Yong Lu³  Xinghui Wu⁴  BaoJun Yu⁶  Ronglin Chen⁷  JieFu Lu⁸  Huasheng Tong⁴ 

[1] The 3rd Xiangya Hospital, Central South University, Department of Critical Care Medicine and Hematology;Department of Intensive Care Unit & Infection Prevention and Control, The Second People‘s Hospital of Shenzhen;Department of Critical Care Medicine, The First People’s Hospital of Chenzhou;Department of Graduate School, Southern Medical University;Department of Intensive Care Unit, General Hospital of Southern Theatre Command of PLA;Department of Intensive Care Unit, Baoan District People’s Hospital;Department of Critical Care Medicine, Longgang District Central Hospital;Department of Intensive Care Unit, The First People’s Hospital of Foshan

关键词: Heatstroke;    Platelet;    NOD-like receptor;    Pyroptosis;    Reactive oxygen species;    NLRP3 inflammasome;   

DOI  :  10.7717/peerj.13799

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

BackgroundThrombocytopenia, an early common complication in heatstroke (HS), has been widely considered as a mortality predictor of HS. The mechanism underlying thrombocytopenia in HS remains unknown. It is not known whether NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is activated in HS platelet, which, in turn, induces platelet activation and thrombocytopenia. This study tried to clarify the activation of the NOD-like receptor signaling pathway under HS conditions and investigate its roles in mediating HS-induced thrombocytopenia.MethodsRat HS models were established in a certain ambient temperature and humidity. Platelets, isolated from blood, were counted and CD62P, an index of platelet activation, was measured by flow cytometry in all rats. The colocalization of NLRP3 inflammasome in platelet was detected by confocal fluorescence microscopy. Mitochondrial-derived reactive oxygen species (ROS) was detected using the molecular probes. Plasma HMGB1 and IL-1β levels were measured by ELISA.ResultsPlatelet activation, showed by upregulated CD62P, and thrombocytopenia were observed in HS rats. HS activated the NLRP3 inflammasome, which was induced by elevated levels of ROS, while the upregulated CD62P and thrombocytopenia triggered by NLRP3 inflammasome were attributed to the high mobility group box protein 1 (HMGB1) inplasma. Moreover, inhibition of the NOD-like receptor signaling pathway in rats with HS suppressed platelet activation and the decline of platelet count. Similar results were obtained when the receptor toll-like receptor 4 (TLR4)/advanced glycation end product (RAGE) was blocked.ConclusionsThe NOD-like receptor signaling pathway induces platelet activation and thrombocytopenia in HS rats. These findings suggested that the NLRP3 inflammasome might be the potential target for HS treatment.

【 授权许可】

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