A self-organized actomyosin drives multiple intercellular junction disruption and directly promotes neutrophil recruitment in lipopolysaccharide-induced acute lung injury
A self-organized actomyosin drives multiple intercellular junction disruption and directly promotes neutrophil recruitment in lipopolysaccharide-induced acute lung injury
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在脂多糖诱导的急性肺损伤中，自组织肌动球蛋白驱动多个细胞间连接破坏并直接促进中性粒细胞募集
DOI：
10.1096/fj.201701506rr
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发表时间：
2018-11-01
期刊：
影响因子：
4.8
通讯作者：
Lu, Kaizhi
中科院分区：
文献类型：
--
作者：
Chen, Bing;Yang, Zhen;Lu, Kaizhi
急性肺损伤（ALI）以血管完整性破坏和中性粒细胞募集为特征，与高发病率和死亡率相关。增强的肌动球蛋白组装有助于内皮细胞接触功能障碍。然而，肌动球蛋白组装在ALI中的作用和机制尚不完全清楚。本研究探讨了内毒素（LPS）诱导的大鼠急性肺损伤（ALI）模型中肌动球蛋白的动态变化及其作用。LPS给药后3 d内，肺E-cadherin、血管内皮-cadherin、occludin、myosin phosphatase target subunit 1和thymosin 4的水平降低，中性粒细胞的数量和活性以及肌动球蛋白、p-相关蛋白激酶、p-肌球蛋白轻链激酶和profilin 1的水平升高，然后，这些变化在接下来的4 d内恢复。这与肺组织学、血管通透性、水肿和血清IL-6和TNF-α水平的改变一致。直接或间接抑制增加的F-肌动蛋白或肌球蛋白组装改善细胞间连接分子的减少，中性粒细胞的活化和迁移，以及肺损伤的程度。此外，中性粒细胞活化进一步促进肌动球蛋白组装，加重肺损伤。总之，自组织肌动球蛋白的增强有助于肺泡-毛细血管屏障破坏和炎症反应中的中性粒细胞募集，这是ALI的潜在治疗靶点。Chen，B.，杨志，杨，C.，秦伟，顾，J.，Hu，C.，陈安，宁，J.，Yi，B.，Lu，K.脂多糖诱导的急性肺损伤中自组织肌动球蛋白驱动多个细胞间连接破坏并直接促进中性粒细胞募集
Acute lung injury (ALI), with the hallmarks of vascular integrity disruption and neutrophil recruitment, is associated with high morbidity and mortality. Enhanced actomyosin assembly contributes to endothelial cell contact dysfunction. However, the roles and mechanisms of actomyosin assembly in ALI are not totally clear. We investigated the dynamic alterations and roles of actomyosin in ALI in vivo and in vitro models induced by LPS. Pulmonary levels of E-cadherin, vascular endothelial-cadherin, occludin, myosin phosphatase target subunit 1, and thymosin 4 were decreased, and the number and activity of neutrophils and the levels of actomyosin, p--associated protein kinase, p-myosin light-chain kinase, and profilin1 were increased within 3 d after LPS administration, and then, those alterations were recovered within the next 4 d, which was consistent with the alterations of lung histology, vascular permeability, edema, and serum levels of IL-6 and TNF-. Direct or indirect inhibition of increased F-actin or myosin assembly ameliorated the reduction of intercellular junction molecules, the activation and migration of neutrophils, and the degree of lung injury. Moreover, neutrophil activation further promoted actomyosin assembly and aggravated lung injury. Conclusively, the enhancement of self-organized actomyosin contributes to alveolar-capillary barrier disruption and neutrophil recruitment in inflammatory response, which is a potential therapeutic target for ALI.Chen, B., Yang, Z., Yang, C., Qin, W., Gu, J., Hu, C., Chen, A., Ning, J., Yi, B., Lu, K. A self-organized actomyosin drives multiple intercellular junction disruption and directly promotes neutrophil recruitment in lipopolysaccharide-induced acute lung injury.