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Pyroptotic Macrophage-Derived Microvesicles Accelerate Formation of Neutrophil Extracellular Traps via GSDMD-N-expressing Mitochondrial Transfer during Sepsis.
Kuang, Liangjian; Wu, Yongjian; Shu, Jingxian; Yang, Jingwen; Zhou, Haibo; Huang, Xi.
Afiliación
  • Kuang L; Center for Infection and Immunity and Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong Province, 519000, China.
  • Wu Y; Center for Infection and Immunity and Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong Province, 519000, China.
  • Shu J; Center for Infection and Immunity and Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong Province, 519000, China.
  • Yang J; The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, Guangdong Province, 511518, China.
  • Zhou H; The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, Guangdong Province, 511518, China.
  • Huang X; Center for Infection and Immunity and Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong Province, 519000, China.
Int J Biol Sci ; 20(2): 733-750, 2024.
Article en En | MEDLINE | ID: mdl-38169726
ABSTRACT
Macrophage pyroptosis and neutrophil extracellular traps (NETs) play a critical role in sepsis pathophysiology; however, the role of macrophage pyroptosis in the regulation of NETs formation during sepsis is unknown. Here, we showed that macrophages transfer mitochondria to neutrophils through microvesicles following pyroptosis; this process induces mitochondrial dysfunction and triggers the induction of NETs formation through mitochondrial reactive oxygen species (mtROS)/Gasdermin D (GSDMD) axis. These pyroptotic macrophage-derived microvesicles can induce tissues damage, coagulation, and NETs formation in vivo. Disulfiram partly inhibits these effects in a mouse model of sepsis. Pyroptotic macrophage-derived microvesicles induce NETs formation through mitochondrial transfer, both in vitro and in vivo. Microvesicles-mediated NETs formation depends on the presence of GSDMD-N-expressing mitochondria in the microvesicles. This study elucidates a microvesicles-based pathway for NETs formation during sepsis and proposes a microvesicles-based intervention measure for sepsis management.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Sepsis / Trampas Extracelulares Límite: Animals Idioma: En Revista: Int J Biol Sci Asunto de la revista: BIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Sepsis / Trampas Extracelulares Límite: Animals Idioma: En Revista: Int J Biol Sci Asunto de la revista: BIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China