Department of Critical Care Medicine, The Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Rd., Hangzhou 310009, China.
Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
Int J Mol Sci. 2023 Mar 7;24(6):5125. doi: 10.3390/ijms24065125.
Acute respiratory distress syndrome (ARDS) threatens the survival of critically ill patients, the mechanisms of which are still unclear. Neutrophil extracellular traps (NETs) released by activated neutrophils play a critical role in inflammatory injury. We investigated the role of NETs and the underlying mechanism involved in acute lung injury (ALI). We found a higher expression of NETs and cyclic GMP-AMP synthase-stimulator of interferon genes () in the airways, which was reduced by Deoxyribonuclease I (DNase I) in ALI. The administration of the inhibitor H-151 also significantly relieved inflammatory lung injury, but failed to affect the high expression of NETs in ALI. We isolated neutrophils from bone marrow and acquired neutrophils by inducing HL-60 to differentiate. After the PMA interventions, exogenous NETs were obtained from such extracted neutrophils. Exogenous NETs intervention in vitro and in vivo resulted in airway injury, and such inflammatory lung injury was reversed upon degrading NETs with or inhibiting with H-151 as well as siRNA . In conclusion, participates in regulating NETs-mediated inflammatory pulmonary injury, which is expected to be a new therapeutic target for ARDS/ALI.
急性呼吸窘迫综合征（ARDS）威胁重症患者的生存，其机制尚不清楚。激活的中性粒细胞释放的中性粒细胞胞外诱捕网（NETs）在炎症损伤中起关键作用。我们研究了 NETs 及其在急性肺损伤（ALI）中涉及的潜在机制。我们发现气道中 NETs 和环鸟苷酸-腺苷酸合酶-干扰素基因刺激物 () 的表达更高，在 ALI 中被脱氧核糖核酸酶 I（DNase I）降低。抑制剂 H-151 的给药也显著缓解了炎症性肺损伤，但未能影响 ALI 中 NETs 的高表达。我们从骨髓中分离出中性粒细胞，并通过诱导 HL-60 分化获得中性粒细胞。在 PMA 干预后，从提取的中性粒细胞中获得外源性 NETs。体外和体内的外源性 NETs 干预导致气道损伤，而用或抑制 H-151 以及 siRNA 降解 NETs 可逆转这种炎症性肺损伤。总之，参与调节 NETs 介导的炎症性肺损伤，有望成为 ARDS/ALI 的新治疗靶点。
