Benzyl butyl phthalate (BBP) induces lung injury and fibrosis through neutrophil extracellular traps.
Benzyl butyl phthalate (BBP) induces lung injury and fibrosis through neutrophil extracellular traps.
复制标题
DOI：
10.1016/j.envpol.2022.119743
复制
发表时间：
2022-07
影响因子：
8.9
通讯作者：
Weili Wang;Zhenyu Liu;Yu Zhang;Liu Wang;Dongwei Meng;Xueqin Li-;Jingbo Zhang;Yuzhang Wu;Xinyuan Zhou;Guoxiang Liu
中科院分区：
文献类型：
--
作者：
Weili Wang;Zhenyu Liu;Yu Zhang;Liu Wang;Dongwei Meng;Xueqin Li-;Jingbo Zhang;Yuzhang Wu;Xinyuan Zhou;Guoxiang Liu
邻苯二甲酸丁苄酯（BBP）是一种广泛使用的增塑剂，其潜在毒性引起了广泛关注。先前的证据表明，BBP 暴露与哮喘和肺功能受损有关。越来越多的数据表明，中性粒细胞胞外陷阱（NET）是中性粒细胞死亡的一种特殊方式，在呼吸系统疾病的发病机制中发挥着至关重要的作用。然而，BBP 在肺损伤中的免疫毒性作用尚不清楚。在这里，我们的目的是研究 BBP 诱导的 NET 对肺损伤和纤维化的潜在影响。用 BBP 治疗的小鼠表现出明显的肺损伤，伴有肺泡出血、肺水肿和中性粒细胞浸润增加。同时，BBP促进支气管肺泡灌洗液中广泛的中性粒细胞浸润和肺组织中的NETs沉积。此外，BBP 在体外明显触发了 NET 的形成，这通过用髓过氧化物酶和瓜氨酸组蛋白 H3 修饰的网状结构得到证实。此外，BBP 促进中性粒细胞的葡萄糖摄取和 ROS 爆发，在 NET 形成过程中发挥重要作用。此外，我们证明NETs可以促进小鼠肺上皮细胞的纤维化，并在BBP诱导的损伤后观察到显着的肺纤维化。总而言之，我们的研究结果表明，接触 BBP 可能会通过 NET 的形成扰乱先天免疫，从而增加肺损伤和纤维化的风险。
Benzyl butyl phthalate (BBP) is an extensively used plasticizer that has aroused widespread concern about its potential toxicity. Previous evidences demonstrate that BBP exposure is associated with asthma and impaired lung function. Accumulating data indicates that neutrophil extracellular traps (NETs), a particular manner of neutrophil death, play a vital role in the pathogenesis of respiratory diseases. However, the immunotoxicity effects of BBP in lung injury are unclear. Here, we aimed to investigate the potential impacts of BBP-induced NETs on lung injury and fibrosis. Mice treated with BBP exhibited significant lung injury, with alveolar hemorrhage, lung edema and increased neutrophil infiltration. Meanwhile, BBP promoted extensive neutrophil infiltration in bronchoalveolar lavage fluid and NETs deposition in lung tissues. Moreover, BBP clearly triggered NETs formationin vitro, which was confirmed by net-like structures decorated with myeloperoxidase and citrullinated histone H3. Furthermore, BBP fueled glucose uptake and ROS burst of neutrophils playing essential roles during NETs formation. Additionally, we proved that NETs could promote fibrogenesis in murine lung epithelial cells and observed lung fibrosis remarkably after BBP-induced injury. Taken together, our findings indicated that exposure to BBP could increase the risk for lung injury and fibrosis by disturbing innate immunity via NETs formation.