2. Academic Validation
  3. GBP2 upregulated in LPS-stimulated macrophages-derived exosomes accelerates septic lung injury by activating epithelial cell NLRP3 signaling

GBP2 upregulated in LPS-stimulated macrophages-derived exosomes accelerates septic lung injury by activating epithelial cell NLRP3 signaling

  • Int Immunopharmacol. 2023 Oct 7;124(Pt B):111017. doi: 10.1016/j.intimp.2023.111017.
Wenhui Huang 1,  Yue Zhang 1,  Bojun Zheng 2,  Xuguang Ling 3,  Guozhen Wang 4,  Lijuan Li 1,  Wei Wang 1,  Miaoxia Pan 1,  Xu Li 5,  Ying Meng 6
Affiliations

Affiliations

  • 1 Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • 2 Department of Critical Care Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
  • 3 Department of Health Management, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • 4 Department of Emergency Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • 5 Department of Emergency Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China; Ministry of Education, Key Laboratory of Hainan Trauma and Disaster Rescue, College of Emergency and Trauma, Hainan Medical University, Haikou 571199, China. Electronic address: [email protected].
  • 6 Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address: [email protected].
PMID: 37812968 DOI: 10.1016/j.intimp.2023.111017
Abstract

Macrophages infiltration is a crucial factor causing Sepsis-associated acute lung injury (ALI). Accumulating evidence suggests macrophages-alveolar epithelial cells communication is proven to be critical in ALI. However, little is known regarding how activated macrophages regulated sepsis-associated ALI. To explore the role of macrophages-alveolar epithelial cells communication in the ALI process, our data revealed that Lipopolysaccharides-induced macrophages-derived exosomes (L-Exo) induced sepsis-associated ALI and caused alveolar epithelial cells damage. Moreover, Guanylate-binding protein 2 (GBP2) was significantly upregulated in L-Exo, and NLRP3 inflammasomes was the direct target of GBP2. Further experimentation showed that GBP2 inhibition in vitro and in vivo reserves L-Exo effects, while GBP2 overexpression in vitro and in vivo promotes L-Exo effects. These results demonstrated that L-Exo contains excessive GBP2 and promotes inflammation through targeting NLRP3 inflammasomes, which induced alveolar epithelial cells dysfunction and Pyroptosis. These findings demonstrate that L-Exo exerted a deleterious effect on ALI by regulating the GBP2/NLRP3 axis, which might provide new insight on ALI prevention and treatment.

Keywords

Exosomes; GBP2; Macrophages; NLRP3 inflammasomes; Septic lung injury.

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