PM2.5 Exposure in the Respiratory System Induces Distinct Inflammatory Signaling in the Lung and the Liver of Mice

Abstract

Fine particulate matter 2.5 (PM2.5) is a harmful air pollutant currently threatening public health. Although many studies have been performed on the general negative effects of PM2.5 in mice and humans, the migration patterns of various immune cells in response to PM2.5 exposure remain unclear. In this study, we aimed to investigate the immune cell migratory response in the lung and the liver of intratracheally PM2.5-inoculated mice. To investigate the migration trajectory of immune cells in the lung and the liver tissues of mice, we employed microscopic tools including two-photon intravital imaging, histological analysis, and transmission electron microscopy. Our data from two-photon intravital imaging showed that there was no significant difference in the number of infiltrated neutrophils in the lung and the liver of PM2.5-treated mice, compared to the nontreated condition. However, from the histological analysis and the transmission electron microscopy after vascular perfusion to remove intravascular leukocytes, we observed that some leukocytes were frequently observed in the lung and the liver of PM2.5-treated mice. Interestingly, quantification of leukocyte population using flow cytometry showed significant increase of neutrophils and macrophages in the lung, but not much in the liver, 24 h post-PM2.5 treatment. These data imply that two-photon intravital imaging of the lung and the liver actually visualized neutrophils, which were adherent to the luminal side of the vasculature. We then conducted mRNA microarray analysis to further observe how PM2.5 affects gene expression patterns in the lung and the liver. PM2.5 treatment changed the mRNA expression associated with the IL-17 signaling pathway in the lung and changed the mRNA expression associated with metabolic pathways in the liver. In summary, these results suggest that the immune response in the lung is distinctly regulated from that in the liver under acute PM2.5-induced inflammation and that these organs consequently are regulated via distinct signaling pathways.

Fine particulate matter (PM2.5) inhalation-induced alterations in the plasma lipidome as promoters of vascular inflammation and insulin resistance

“…Supporting the idea that lipolysis may be involved are studies showing that exposure to air pollution elevates catecholamines (48)(49)(50), which are potent activators of lipolysis enzymes (51) and could lead to the development of CAP-induced dyslipidemia. The potential involvement of the liver is supported by numerous studies showing that PM 2.5 promotes liver steatosis and fibrosis (52)(53)(54)(55). In addition, we found that biliverdin was elevated in mice exposed to the higher level of CAP, which may suggest some degree of liver damage.…”

Particulate matter causes skin barrier dysfunction

“…We propose that keratinocytes and neutrophils could be the main sources of TNF-α after PM 2.5 exposure. Previous studies reported that PM 2.5 induces the recruitment of neutrophils ( 52 , 53 ), which produces TNF-α ( 54 ). Additionally, we demonstrated that FLG and LOR were inhibited by PM 2.5 , which did not affect IVL .…”

Pharmacological inhibition of PAI-1 alleviates cardiopulmonary pathologies induced by exposure to air pollutants PM2.5

“…Doses of PM 2.5 were selected based on well accepted published literature. 15–21 Group 3: mice were fed with chow containing TM5614 (10 mg/kg) for 6 days and then received PBS (25 μl X2 control) and TM5614 chow. Group 4: mice were fed with chow containing TM5614 (10 mg/kg) for 6 days and then received PM 2.5 (50-200 μg/mouse in 50 μl PBS; 25 μl X2) and TM5614 chow.…”