Journal of Inflammation Research (Jan 2022)

Secretory Autophagosomes from Alveolar Macrophages Exacerbate Acute Respiratory Distress Syndrome by Releasing IL-1β

  • Xu X,
  • Liu X,
  • Dong X,
  • Qiu H,
  • Yang Y,
  • Liu L

Journal volume & issue
Vol. Volume 15
pp. 127 – 140

Abstract

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Xinyi Xu, Xu Liu, Xuecheng Dong, Haibo Qiu, Yi Yang, Ling Liu Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, People’s Republic of ChinaCorrespondence: Yi Yang; Ling LiuJiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, People’s Republic of ChinaEmail [email protected]; [email protected]: Activated alveolar macrophages (AMs) secrete extracellular vesicles and particles to mediate the inflammatory response in the acute respiratory distress syndrome (ARDS) although the underlying mechanisms are poorly understood. This study investigated whether secretory autophagosomes (SAPs) from AMs contribute to the inflammation-mediated lung injury of ARDS.Methods: We first isolated SAPs from cell culture supernatants of RAW264.7 cells and AMs and quantified Interleukin (IL)-1β levels in SAPs. Next, we employed a lipopolysaccharide (LPS)-induced ARDS model to investigate whether SAP-derived IL-1β could exacerbate lung injury. Finally, we used siRNA to knockdown Rab8a, both in vitro and in vivo, to investigate the effect of Rab8a on SAP secretion and lung injury in ARDS.Results: We found that AMs play an important role in ARDS by releasing a novel type of proinflammatory vesicles called SAPs that could exacerbate lung injury. SAPs are characterized as double-membrane vesicles (diameter ∼ 200 nm) with the expression of light chain 3 (LC3). IL-1β in SAPs is the key factor that contributes to the inflammation and lung injury in ARDS. We found that Rab8a is necessary for AMs to release SAPs with IL-1β, and Rab8a knockdown alleviated lung injury in ARDS.Conclusion: This study showed the novel finding that SAPs released from AMs play a vital role in ARDS by promoting an inflammatory response and the underlying mechanism was associated with IL-1β secretion.Keywords: secretory autophagosomes, alveolar macrophages, interlukin-1β, Rab8a, acute respiratory distress syndrome

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