Endothelial cell-derived extracellular vesicles promote sepsis-related acute lung injury by targeting and reprogramming monocytes
Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a common life-threatening critical syndrome with no effective pharmacotherapy. Extracellular vesicles (EVs) are considered as a new way of long-distance communication between cells. Our previous research using an ex vivo perfused human ALI model suggested that endothelial cell-derived EVs (EC-EVs) mediate the development of ALI/ARDS. However, how EC-EVs aggravate lung injury remains largely unknown. Here we demonstrated that EC-EVs released under inflammatory stimulation are preferentially taken up by monocytes and reprogram the differentiation of monocytes towards M1 type macrophage. These findings demonstrate a previously unidentified mechanism by which distant infections could lead to ALI/ARDS, providing novel targets and strategies for the prevention and treatment of sepsis-related ALI/ARDS. Overall design: To further clarify the role of EC-EVs in the development of sepsis-related ARDS, we isolated normal mouse endothelial cell-derived EVs (N-EC-EVs) and used LPS stimulation to simulate the in vivo environment of sepsis (the derived EVs were named L-EC-EVs). The extracted primary mouse bone marrow-derived monocytes were co-incubated with N-EC-EVs or L-EC-EVs for 24 h, and subjected to RNA sequencing.