Neutrophil extracellular traps promote cadmium chloride-induced lung injury in mice
2019
Wang, Chaoqun | Wei, Zhengkai | Han, Zhen | Wang, Jingjing | Zhang, Xu | Wang, Yanan | Liu, Quan | Yang, Zhengtao
Cadmium (Cd) is a ubiquitous toxic heavy metal derived mainly from industrial processes. In industrialized societies, individuals are exposed to a plethora of sources of Cd pollution. Cd can trigger serious diseases such as rheumatoid arthritis (RA) and chronic obstructive pulmonary disease (COPD) by the over-activating immune system. As an effector mechanism in innate immunity, neutrophil extracellular traps (NETs) not only play an important role in defending against infection but also lead to tissue damage. However, the role of NETs in Cd-induced lung damage process has not been previously studied. In this study, we aimed to investigate the potential effects of Cd-induced NETs on lung injury in vivo and further to clarify the molecular mechanisms of Cd-induced NETs formation. In vivo, Cd treatment destroyed the structural integrity of lung tissue and significantly increased the levels of NETs in the bronchoalveolar lavage fluid (BALF). The known NETs inhibitor DNase I ameliorated pathologic changes and significantly decreased levels of NETs in BALF, which suggesting the curial role of NETs in Cd-induced lung injury. Further investigation showed that Cd could significantly trigger NETs formation, which is composed of DNA backbone decorated with histones (H3) and neutrophils elastase (NE). The inhibitors of NADPH oxidase, ERK1/2 and p38 MAPK-signaling pathways significantly reduced the formation of NETs, and western blotting analysis also showed that Cd significantly increased the phosphorylation of p38 and ERK1/2 signaling pathways. Above results confirmed that NADPH oxidase, ERK1/2 and p38 MAPK-signaling pathways were related to Cd-induced NETs formation. In conclusion, NETs was involved in Cd-induced lung injury, and the mechanisms of Cd-induced NETs formation was via activating NADPH oxidase, ERK1/2 and p38 MAPK-signaling pathways, which might provide a new perspective in Cd-induced lung injury.
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