Bletilla striata polysaccharides alleviate ARDS by inhibiting NETs-induced pyroptosis in pulmonary alveolar macrophage through the PAD4 pathway

Bletilla striata, a traditional Chinese medicine known for its astringent hemostatic and heat-clearing properties, has been traditionally utilized for detoxification. This study aims to explore the potential of Bletilla striata polysaccharides (BSP) in alleviating pneumonia associated with acute respiratory distress syndrome (ARDS) by influencing Neutrophil Extracellular Traps (NETs) as well as NETs-induced alveolar macrophages (AMs) pyroptosis. Results found that BSP demonstrated a significant mitigation effect to lung injury in ARDS mice. It exhibited a notable regulatory effect on neutrophils and macrophages. Specifically, BSP effectively reduced the level of NETs in both lung tissue and the entire body of ARDS mice. It also attenuated the formation of immune thrombosis in the lungs and reduced the incidence of pyroptosis in AMs. Furthermore, in MH-S cells treated with NETs + LPS, which induced pyroptosis, BSP demonstrated significant alleviation of inflammation and pyroptosis. The attenuating effect of BSP was weakened when the GSK484 was introduced to ARDS mice, suggesting the involvement of PAD4 in BSP's mechanism of action. The results demonstrated that BSP has the potential to modulate neutrophil/macrophage homeostasis via the PAD4 pathway, leading to a reduction in NETs levels and alleviation of NETs-induced pyroptosis in alveolar macrophages, alleviating ARDS.