Property-activity relationship between physicochemical properties of PM and their activation of NLRP3 inflammasome.

Air pollution is becoming severe environment factor affecting human health. More and more research has indicated that fine particulate matter (PM) plays a critical role in causing pulmonary inflammation or fibrosis, which potentially is ascribed to the activation of nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome. However, the underlying property-activity relationship between the physicochemical properties of PM and their activation of NLRP3 inflammasome remains unclear. Herein, various ways, such as metal chelation, organic extraction, ROS consumption, charge neutralization and particle dispersion, were applied to interfere with the effects of metal ion, polycyclic aromatic hydrocarbons (PAHs), reactive oxygen species (ROS), charge and size. It was found that aggregated size and PAHs could activate the NLRP3 inflammasome through lysosome rupture and potassium efflux, respectively. Metal ion, PAHs and surface ROS could also activate the NLRP3 inflammasome through mitochondrial ROS production. However, neutralization of PM with the negative surface charge could not relieve the activation of NLRP3 inflammasome. Furthermore, oropharyngeal aspiration of various modified PM were adopted to explore their effects on lung fibrosis, which showed the consistent results with those in cellular levels. Removal of metal ion, PAHs and ROS as well as reduction of size of PM could reduce collagen deposition in the lung tissue of mice, while the charge neutralization of PM increased this collagen deposition. This study provides great insights to clarify the property-activity relationship of PM.