N-acetylcysteine alleviates fine particulate matter (PM2.5)-induced lung injury by attenuation of ROS-mediated recruitment of neutrophils and Ly6Chigh 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 Ly6Chigh 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 μg/100 μl/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-α 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 Ly6Chigh and Ly6Clow 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 Ly6Chigh, but not Ly6Clow monocytes, into lung alveoli. Treatment with NAC via the intratracheal spray significantly attenuated the recruitment of neutrophils and Ly6Chigh 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 Ly6Chigh monocytes, and production of inflammatory proteins. NAC treatment alleviated PM2.5-induced lung injury by attenuating the ROS-mediated recruitment of neutrophils and Ly6Chigh monocytes and lung inflammation.