Department of Immunology, Mie University, Graduate School of Medicine Mie, Edobashi 2-174, Tsu, Mie 514-8507, Japan.
Department of Diabetes and Endocrinology, Mie University, Graduate School of Medicine Mie, Edobashi 2-174, Tsu, Mie 514-8507, Japan.
Int J Mol Sci. 2019 Mar 2;20(5):1082. doi: 10.3390/ijms20051082.
Acute lung injury is a fatal disease characterized by inflammatory cell infiltration, alveolar-capillary barrier disruption, protein-rich edema, and impairment of gas exchange. Protein S is a vitamin K-dependent glycoprotein that exerts anticoagulant, immunomodulatory, anti-inflammatory, anti-apoptotic, and neuroprotective effects. The aim of this study was to evaluate whether human protein S inhibits cell apoptosis in acute lung injury. Acute lung injury in human protein S transgenic and wild-type mice was induced by intratracheal instillation of lipopolysaccharide. The effect of human protein S on apoptosis of lung tissue cells was evaluated by Western blotting. Inflammatory cell infiltration, alveolar wall thickening, myeloperoxidase activity, and the expression of inflammatory cytokines were reduced in human protein S transgenic mice compared to the wild-type mice after lipopolysaccharide instillation. Apoptotic cells and caspase-3 activity were reduced while phosphorylation of extracellular signal-regulated kinase was enhanced in the lung tissue from human protein S transgenic mice compared to wild-type mice after lipopolysaccharide instillation. The results of this study suggest that human protein S is protective in lipopolysaccharide-induced acute lung injury by inhibiting apoptosis of lung cells.
急性肺损伤是一种致命性疾病，其特征为炎症细胞浸润、肺泡毛细血管屏障破坏、富含蛋白的水肿以及气体交换受损。蛋白 S 是一种维生素 K 依赖性糖蛋白，具有抗凝、免疫调节、抗炎、抗凋亡和神经保护作用。本研究旨在评估人蛋白 S 是否抑制急性肺损伤中的细胞凋亡。通过气管内滴注脂多糖诱导人蛋白 S 转基因和野生型小鼠的急性肺损伤。通过 Western blot 评估人蛋白 S 对肺组织细胞凋亡的影响。与野生型小鼠相比，人蛋白 S 转基因小鼠在脂多糖滴注后炎症细胞浸润、肺泡壁增厚、髓过氧化物酶活性和炎症细胞因子的表达减少。与野生型小鼠相比，在脂多糖滴注后，人蛋白 S 转基因小鼠的肺组织中凋亡细胞和 caspase-3 活性减少，而细胞外信号调节激酶的磷酸化增强。本研究结果提示，人蛋白 S 通过抑制肺细胞凋亡对脂多糖诱导的急性肺损伤具有保护作用。
