Property-activity relationship between physicochemical properties of PM2.5 and their activation of NLRP3 inflammasome

Runxiao Zheng; Panpan Song; Yunyun Wu; Yanjing Wang; Xiaoqing Han; Jiao Yan; Xiaqing Wu; Haiyuan Zhang

doi:10.1016/j.impact.2022.100380

Property-activity relationship between physicochemical properties of PM_2.5 and their activation of NLRP3 inflammasome

NanoImpact. 2022 Jan:25:100380. doi: 10.1016/j.impact.2022.100380. Epub 2022 Jan 11.

Authors

Runxiao Zheng¹, Panpan Song², Yunyun Wu³, Yanjing Wang², Xiaoqing Han⁴, Jiao Yan⁴, Xiaqing Wu², Haiyuan Zhang⁵

Affiliations

¹ Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, Jilin, China; University of Science and Technology of China, Hefei, China; Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, China.
² Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, Jilin, China; University of Science and Technology of China, Hefei, China.
³ School of Chemistry and Life Science, Changchun University of Technology, Changchun, 130012, Jilin, China.
⁴ Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, Jilin, China.
⁵ Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, Jilin, China; University of Science and Technology of China, Hefei, China. Electronic address: zhangh@ciac.ac.cn.

PMID: 35559886
DOI: 10.1016/j.impact.2022.100380

Abstract

Air pollution is becoming severe environment factor affecting human health. More and more research has indicated that fine particulate matter (PM_2.5) 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_2.5 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_2.5 with the negative surface charge could not relieve the activation of NLRP3 inflammasome. Furthermore, oropharyngeal aspiration of various modified PM_2.5 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_2.5 could reduce collagen deposition in the lung tissue of mice, while the charge neutralization of PM_2.5 increased this collagen deposition. This study provides great insights to clarify the property-activity relationship of PM_2.5.

Keywords: Lung fibrosis; NLRP3 inflammasome; PM(2.5); Property-activity relationship.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Air Pollution*
Animals
Inflammasomes
Mice
NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
Particulate Matter
Polycyclic Aromatic Hydrocarbons*
Reactive Oxygen Species / metabolism

Substances

Inflammasomes
NLR Family, Pyrin Domain-Containing 3 Protein
Nlrp3 protein, mouse
Particulate Matter
Polycyclic Aromatic Hydrocarbons
Reactive Oxygen Species