Int J Biol Sci 2022; 18(4):1521-1538. doi:10.7150/ijbs.66477 This issue Cite
Research Paper
1. Thoracic Surgery Laboratory, The First College of Clinical Medicine, Xuzhou Medical University, Xuzhou 221006, Jiangsu Province, China.
2. Department of Thoracic Surgery, Affiliated Hospital of Xuzhou Medical University, 99 West Huaihai Road, Xuzhou 221006, Jiangsu, China.
3. Department of Thoracic and Cardiovascular Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China.
4. Department of Clinical Medical Engineering, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
5. Public Experimental Research Center, Xuzhou Medical University, Xuzhou 221006, Jiangsu Province, China.
*These authors contributed equally to this work.
The occurrence and development of acute lung injury (ALI) involve a variety of pathological factors and complex mechanisms. How pulmonary cells communicate with each other and subsequently trigger an inflammatory cascade remains elusive. Extracellular vesicles (EVs) are a critical class of membrane-bound structures that have been widely investigated for their roles in pathophysiological processes, especially in immune responses and tumor progression. Most of the current knowledge of the functions of EVs is related to functions derived from viable cells (e.g., microvesicles and exosomes) or apoptotic cells (e.g., apoptotic bodies); however, there is limited understanding of the rapidly progressing inflammatory response in ALI. Herein, a comprehensive analysis of micron-sized EVs revealed a mass production of 1-5 μm pyroptotic bodies (PyrBDs) release in the early phase of ALI induced by lipopolysaccharide (LPS). Alveolar macrophages were the main source of PyrBDs in the early phase of ALI, and the formation and release of PyrBDs were dependent on caspase-1. Furthermore, PyrBDs promoted the activation of epithelial cells, induced vascular leakage and recruited neutrophils through delivery of damage-associated molecular patterns (DAMPs). Collectively, these findings suggest that PyrBDs are mainly released by macrophages in a caspase-1-dependent manner and serve as mediators of LPS-induced ALI.
Keywords: extracellular vesicles, pyroptosis, acute lung injury, alveolar macrophage, caspase-1