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
  • 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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