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Int J Biol Sci 2024; 20(2):733-750. doi:10.7150/ijbs.87646 This issue Cite

Research Paper

Pyroptotic Macrophage-Derived Microvesicles Accelerate Formation of Neutrophil Extracellular Traps via GSDMD-N-expressing Mitochondrial Transfer during Sepsis

Liangjian Kuang1*, Yongjian Wu1*, Jingxian Shu1*, Jingwen Yang2, Haibo Zhou2, Xi Huang1,2✉

1. 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.
2. The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, Guangdong Province, 511518, China.
*These authors contributed equally to this work.

✉ Corresponding author: Xi Huang, Professor, Center for Infection and Immunity, The Fifth Affiliated Hospital of Sun Yat-sen University, China. Email: huangxi6sysu.edu.cn.

Citation:
Kuang L, Wu Y, Shu J, Yang J, Zhou H, Huang X. Pyroptotic Macrophage-Derived Microvesicles Accelerate Formation of Neutrophil Extracellular Traps via GSDMD-N-expressing Mitochondrial Transfer during Sepsis. Int J Biol Sci 2024; 20(2):733-750. doi:10.7150/ijbs.87646. https://www.ijbs.com/v20p0733.htm
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Abstract

Graphic 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.

Keywords: Pyroptosis, microvesicles, neutrophil extracellular traps, mitochondrial transfer, sepsis

Citation styles

APA
Kuang, L., Wu, Y., Shu, J., Yang, J., Zhou, H., Huang, X. (2024). Pyroptotic Macrophage-Derived Microvesicles Accelerate Formation of Neutrophil Extracellular Traps via GSDMD-N-expressing Mitochondrial Transfer during Sepsis. International Journal of Biological Sciences, 20(2), 733-750. https://doi.org/10.7150/ijbs.87646.

ACS
Kuang, L.; Wu, Y.; Shu, J.; Yang, J.; Zhou, H.; Huang, X. Pyroptotic Macrophage-Derived Microvesicles Accelerate Formation of Neutrophil Extracellular Traps via GSDMD-N-expressing Mitochondrial Transfer during Sepsis. Int. J. Biol. Sci. 2024, 20 (2), 733-750. DOI: 10.7150/ijbs.87646.

NLM
Kuang L, Wu Y, Shu J, Yang J, Zhou H, Huang X. Pyroptotic Macrophage-Derived Microvesicles Accelerate Formation of Neutrophil Extracellular Traps via GSDMD-N-expressing Mitochondrial Transfer during Sepsis. Int J Biol Sci 2024; 20(2):733-750. doi:10.7150/ijbs.87646. https://www.ijbs.com/v20p0733.htm

CSE
Kuang L, Wu Y, Shu J, Yang J, Zhou H, Huang X. 2024. Pyroptotic Macrophage-Derived Microvesicles Accelerate Formation of Neutrophil Extracellular Traps via GSDMD-N-expressing Mitochondrial Transfer during Sepsis. Int J Biol Sci. 20(2):733-750.

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