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  3. Lead activates neutrophil degranulation to induce early myocardial injury in mice

Lead activates neutrophil degranulation to induce early myocardial injury in mice

  • Ecotoxicol Environ Saf. 2023 Nov 18:268:115694. doi: 10.1016/j.ecoenv.2023.115694.
Yanjun Wu 1,  Hongmei Huang 2,  Jiayun Wu 3,  Yiru Qin 4,  Na Zhao 5,  Baowei Chen 6,  Qiying Nong 7,  Yongshun Huang 8,  Ligang Hu 9
Affiliations

Affiliations

  • 1 Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510300, China; School of Public Health, Southern Medical University, Guangzhou 510505, China.
  • 2 Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510300, China; School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
  • 3 Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510300, China; School of Public Health, Guangdong Pharmaceutical University, Guangzhou 510310, China.
  • 4 Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510300, China.
  • 5 Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510300, China; School of Public Health, Southern Medical University, Guangzhou 510505, China; School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
  • 6 Southern Marine Science and Engineering Guangdong Laboratory, School of Marine Sciences, Sun Yat-Sen University, Zhuhai 519082, China.
  • 7 Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510300, China. Electronic address: nongqy@mail3.sysu.edu.cn.
  • 8 Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510300, China; School of Public Health, Southern Medical University, Guangzhou 510505, China; School of Public Health, Sun Yat-sen University, Guangzhou 510080, China; School of Public Health, Guangdong Pharmaceutical University, Guangzhou 510310, China. Electronic address: ysh_huang@126.com.
  • 9 State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
PMID: 37984289 DOI: 10.1016/j.ecoenv.2023.115694
Abstract

Lead (Pb) is a pervasive toxic metal contaminant associated with a high risk of myocardial injury. However, the precise mechanism underlying Pb-induced myocardial injury has yet to be fully elucidated. In this study, a murine model of Pb exposure (0, 1, 5, and 10 mg/kg) was employed to investigate the involvement of neutrophil degranulation in the induction of myocardial injury. Notably, serum levels of cardiac troponin I (cTnI) and creatine kinase-MB (CK-MB) increased significantly in Pb-exposed mice, whereas cTnI levels in cardiomyocytes decreased, suggesting that Pb exposure may cause early myocardial injury. Moreover, Pb exposure was found to promote neutrophil degranulation, as evidenced by elevated myeloperoxidase (MPO) and neutrophil Elastase (NE) concentrations in both the serum of Pb-exposed workers and Pb-exposed mice, as well as the extracellular supernatant of neutrophils following exposure. However, we found that serum level of cTnI enhanced by Pb exposure is associated with increased NE levels in the serum, but not with MPO levels. Upon treatment with NE inhibitor (sivelestat), the serum level of cTnI markedly reduced in Pb-exposed mice, we found that early myocardial injury is associated with NE levels in the serum. At the molecular level, western blotting analysis revealed an upregulation of ERK1/2 expression in vitro following Pb exposure, suggesting that the activation of the ERK1/2 signaling pathway may underlie the participation of neutrophil degranulation in Pb-induced myocardial injury. In summary, our findings demonstrate that Pb exposure can initiate early myocardial injury by promoting the neutrophil degranulation process, thereby highlighting the potential role of this process in the pathogenesis of Pb-associated myocardial injury.

Keywords

Lead exposure; Myeloperoxidase; Myocardial injury; Neutrophil degranulation; Neutrophil elastase.

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