Journal
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
Volume 239, Issue -, Pages -Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ecoenv.2022.113632
Keywords
Fine particulate matter; PM-induced lung injury; Ly6C(high) monocyte; N-acetylcysteine
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Funding
- Chiayi Chang Gung Me-morial Hospital, Taiwan [CMRPG6J0121]
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This study found that PM2.5-induced lung injury is caused by oxidative stress leading to the recruitment of neutrophils and Ly6C(high) monocytes, and production of inflammatory proteins. Treatment with NAC alleviated PM2.5 induced lung injury by attenuating the ROS-mediated recruitment of neutrophils and Ly6C(high) monocytes and lung inflammation.
Background: Exposure to particulate matter (PM) may contribute to lung inflammation and injury. The therapeutic effect of N-acetylcysteine (NAC), a well-known antioxidant, with regards to the prevention and treatment of fine PM (PM2.5)-induced lung injury is poorly understood. This study aimed to determine the effect of PM2.5 on the recruitment of neutrophils and Ly6C(high) monocytes into lung alveoli and the production of proinflammatory proteins by stimulating the generation of reactive oxygen species (ROS), and to investigate the therapeutic effect of NAC on PM2.5-induced lung injury. Methods: C57BL/6 mice were exposed to a single administration of PM2.5 (200 mu g/100 mu l/mouse) or phosphate-buffered saline (control) via intratracheal instillation. The mice were injected intratracheally via a microsprayer aerosolizer with NAC (20 or 40 mg/kg) 1 h before PM2.5 instillation and 24 h after PM2.5 instillation. Total protein, VEGF, IL-6, and TNF-alpha in bronchoalveolar lavage fluid (BALF) were measured. Oxidative stress was evaluated by determining levels of malondialdehyde (MDA) and nitrite in BALF. Flow cytometric analysis was used to identify and quantify neutrophils and Ly6C(high) and Ly6C(low) monocyte subsets. Results: Neutrophil count, total protein, and VEGF content in BALF significantly increased after PM2.5 exposure and reached the highest level on day 2. Increased levels of TNF-alpha, IL-6, nitrite, and MDA in BALF were also noted. Flow cytometric analysis showed increased recruitment of neutrophils and Ly6C(high), but not Ly6C(low) monocytes, into lung alveoli. Treatment with NAC via the intratracheal spray significantly attenuated the recruitment of neutrophils and Ly6C(high) monocytes into lung alveoli in PM2.5-treated mice in a dose-dependent manner. Furthermore, NAC significantly attenuated the production of total protein, VEGF, nitrite, and MDA in the mice with PM2.5-induced lung injury in a dose-dependent manner. Conclusion: PM2.5-induced lung injury caused by the generation of oxidative stress led to the recruitment of neutrophils and Ly6C(high) monocytes, and production of inflammatory proteins. NAC treatment alleviated PM2.5 induced lung injury by attenuating the ROS-mediated recruitment of neutrophils and Ly6C(high) monocytes and lung inflammation.
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