Regulatory roles of SP-A and exosomes in pneumonia-induced acute lung and kidney injuries

Frontiers in Immunology

Immunology

Junping Guo¹  Salma Mahmoud¹  Gautam Vanga¹  Tianyi Liu¹  Yunhe Xiong¹  Osama Abdel-Razek¹  Wanwen Xu¹  Weichuan Xiong¹  Guirong Wang²  Xinghua Chen³ 

[1] Department of Surgery, SUNY Upstate Medical University, Syracuse, NY, United States;Department of Surgery, SUNY Upstate Medical University, Syracuse, NY, United States;Department of Microbiology and Immunology, SUNY Upstate Medical University, Syracuse, NY, United States;Department of Surgery, SUNY Upstate Medical University, Syracuse, NY, United States;Department of Nephrology, Wuhan University, Renmin Hospital, Wuhan, Hubei, China;

关键词: acute kidney injury (AKI);    exosomes;    innate immunity;    renal tubular epithelial cells;    surfactant protein A (SP-A);   

DOI  :  10.3389/fimmu.2023.1188023

 received in 2023-03-16, accepted in 2023-05-02,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionPneumonia-induced sepsis can cause multiple organ dysfunction including acute lung and kidney injury (ALI and AKI). Surfactant protein A (SP-A), a critical innate immune molecule, is expressed in the lung and kidney. Extracellular vesicles like exosomes are involved in the processes of pathophysiology. Here we tested one hypothesis that SP-A regulates pneumonia-induced AKI through the modulation of exosomes and cell death.MethodsWild-type (WT), SP-A knockout (KO), and humanized SP-A transgenic (hTG, lung-specific SP-A expression) mice were used in this study.ResultsAfter intratracheal infection with Pseudomonas aeruginosa, KO mice showed increased mortality, higher injury scores, more severe inflammation in the lung and kidney, and increased serum TNF-α, IL-1β, and IL-6 levels compared to WT and hTG mice. Infected hTG mice exhibited similar lung injury but more severe kidney injury than infected WT mice. Increased renal tubular apoptosis and pyroptosis in the kidney of KO mice were found when compared with WT and hTG mice. We found that serum exosomes from septic mice cause ALI and AKI through mediating apoptosis and proptosis when mice were injected intravenously. Furthermore, primary proximal tubular epithelial cells isolated from KO mice showed more sensitivity than those from WT mice after exposure to septic serum exosomes.DiscussionCollectively, SP-A attenuates pneumonia-induced ALI and AKI by regulating inflammation, apoptosis and pyroptosis; serum exosomes are important mediators in the pathogenesis of AKI.

【 授权许可】

Unknown   
Copyright © 2023 Chen, Guo, Mahmoud, Vanga, Liu, Xu, Xiong, Xiong, Abdel-Razek and Wang