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Research indicates that autologous alveolar epithelial cell-derived exosomes possess a natural tropism for the pulmonary immune microenvironment, enabling precise localization and regulation of target cells such as alveolar macrophages ( in situ regeneration of the damaged barrier and the reconstruction of microenvironmental homeostasis, providing a highly potential nanomedicine solution for conquering the clinical challenge of sepsis-associated ARDS ( 5 Macrophage-derived exosomes: the command center of immunometabolic reprogramming Alveolar macrophages (AMs) are not only the first line of defense in pulmonary immune defense but also key cells that perceive danger signals and initiate responses during the pathological progression of sepsis-associated ARDS ( 5.1 Glycolytic fueling and intercellular transmission of metabolic reprogramming In the early stages of sepsis-induced ARDS, AMs undergo drastic metabolic reprogramming, rapidly shifting from using oxidative phosphorylation for energy production to aerobic glycolysisthe Warburg effectto meet the energy and biosynthetic demands for the rapid synthesis of inflammatory mediators ( During the pathological process of acute lung injury, M1-polarized macrophages undergo significant glycolytic reprogramming, leading to the significant upregulation and accumulation of key intracellular glycolytic enzymes such as pyruvate kinase M2 (PKM2) and hexokinase 2 (HK2) ( IL-1 , initiating their transcriptional expression ( As the disease enters the recovery phase or is induced by an anti-inflammatory microenvironment, alveolar macrophages transform toward the M2 phenotype, and the exosomes they secrete become rich in anti-inflammatory and pro-reparative molecules, becoming key signal carriers for maintaining pulmonary homeostasis and initiating tissue regeneration

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doi: 10.1089/ars.2019.7880 28 LiHLiuHChenZZhaoRWangQRanMet al