Exposure scenario: Another important factor determining the toxic effects of PM2.5 and possible mechanisms involved☆
Graphical abstract
Introduction
Air pollution by ambient particulate matter has become one of the most serious environmental and public health challenges in many developing and developed countries. In particular, increasing airborne fine particulate matter with an aerodynamic diameter less than 2.5 μm (PM2.5) has a profound impact on public health (Zhang et al., 2015). In some areas of north China, the annual mean concentration of PM2.5 has reached about 100 μg/m3; over the last few years (Xie et al., 2015, Zheng et al., 2015). People living in these long-polluted areas are more likely to be in a long-term, slightly polluted PM2.5 exposure scenario (repeated exposure). In addition, acute haze episodes or smog events with high concentrations of PM2.5 (more than 500 μg/m3, sometimes over 1000 μg/m3) now occur frequently in some areas (Guan et al., 2014). Therefore, the population may be subjected to two distinct PM2.5 exposure scenarios, repeated low-level and short-term high-level exposure, with different health effects.
Exposure to PM2.5, including both acute exposure at extremely high levels and repeated exposure at lower levels, is strongly associated with many pulmonary diseases (Lelieveld et al., 2015, Young et al., 2014). Previous studies have indicated that even short-term (several hours) exposure to extremely high levels of PM2.5 can induce acute inflammation of the respiratory tract and acute exacerbation of cardiopulmonary diseases, such as asthma and acute paroxysm of chronic bronchitis (Khafaie et al., 2016, Marino et al., 2015, Yamauchi et al., 2016). Accumulating evidence has demonstrated that long-term low-level PM2.5 exposure can also contribute to a variety of chronic pulmonary diseases, including chronic obstructive pulmonary disease (COPD), fibrosis and even lung cancer (Benmerad et al., 2015, Hamra et al., 2014, Khafaie et al., 2016).
However, the exact mechanisms underlying PM2.5-induced pulmonary diseases are not well-known, and it is unclear whether PM2.5 induces similar toxicity mechanisms under different exposure scenarios. Most in vitro experiments have focused on the adverse effects of short-term PM2.5 exposure to high concentrations (Ding et al., 2014, Vattanasit et al., 2014, Yang et al., 2015), but the toxicity mechanisms obtained may be different from those induced by long-term low-level exposure and thus do not provide an accurate model of PM2.5-induced disease. Recently, some researchers have posited that the PM2.5 response exhibits hormesis, defined as an inverted U-shaped or J-shaped dose-response relationship (Cox, 2012). Several studies have demonstrated that long-term low-level exposure to particles or nanoparticles elicits dissimilar biological responses compared to short-term high-level exposure (Vales et al., 2015, Zhou et al., 2016). All these findings suggest that in addition to particle size and chemical composition, exposure scenario may be an important factor determining the toxic effects of PM2.5.
ROS-mediated oxidative stress is believed to play a crucial role in PM2.5-induced cytotoxicity (Xia et al., 2007), and the kinetics of ROS accumulation depend on the characteristics of PM2.5 exposure, such as duration and particle concentration. Intracellular ROS could thus serve as a biological signal to elicit different responses, including reparative/adaptive and pathogenic responses (Dioni et al., 2011, Schumacker, 2015, Shadel and Horvath, 2015). It has been reported that ROS-induced oxidative stress injuries, such as DNA damage and repair, cell death, inflammation and epigenetic regulation, vary with different PM2.5 exposure scenarios (Gao et al., 2016, Longhin et al., 2013, Zhou et al., 2016). The hypothesis addressed in the present study is that even brief exposure to higher concentrations of PM2.5 induces extensive ROS-mediated oxidative damage that overwhelms endogenous defense mechanisms, causing injury and metabolic collapse in a short time, while repeated exposure to low PM2.5 levels causes chronic and low-grade enhancement of ROS, which triggers cycles of perturbation/damages and repairs mediated by adaptive responses.
We thus compared the responses of the human bronchial epithelial cell line BEAS-2B to two distinct PM2.5 exposure scenarios to examine whether exposure is an important parameter determining the health effects of PM2.5. The prospective findings of our study could offer new insight into the pathogenesis of diseases caused by PM2.5 exposure.
Section snippets
Preparation of PM2.5 suspension and cell exposure
The PM2.5 used in this study was collected from Wuhan, China. The specific methods for PM2.5 collection, extraction, and characterization, and the detailed characteristics of the sampling site were described in our previous report (Yuan et al., 2015, Zhou et al., 2016). PM2.5 suspensions were freshly prepared before each application. Briefly, PM2.5 was re-suspended in Dulbecco's Modified Eagle's Medium (DMEM, Gibco, USA) containing 2% fetal bovine serum (FBS, Gibco) and the solution was
Exposure models
The doses used in this study are based on real-world exposure scenarios revealed by MPPD software (de Winter-Sorkina and Cassee, 2003, Gangwal et al., 2011). Air quality is closely associated with PM2.5 concentration. The concentrations of 100, 200, 500 and 1000 μg/m3 were corresponding to lightly, moderately, heavily, and severely polluted, respectively. The MPPD software provides more precise calculations of the actual deposition, clearance, and retention of PM2.5 on epithelium. The total
Discussion
The increasing severity of air pollution in certain regions, especially airborne fine particulate matter (PM2.5), is strongly linked to the incidence of respiratory diseases (Coogan et al., 2012, Hamra et al., 2014, Rice et al., 2016). In recent years, numerous studies have characterized the toxicity of PM2.5 and explored the underlying cellular mechanisms to provide a detailed explanation of the initiation and development of PM2.5-induced diseases. However, there is still no consensus on PM2.5
Conclusion
In summary, one of most intriguing implications of our data is that PM2.5 can cause distinct toxic effects under different exposure conditions. Acute high-dose exposure overwhelms anti-oxidative capacity and the ability to clear damaged constituents by autophagic flux, resulting in necrosis and inflammation. In contrast, most cells may have sufficient capacity to survive mild sustained exposure, while the few dying cells are cleared by apoptosis, obviating inflammation. However, accumulation of
Funding sources
This work was supported by National Key Basic Research Program of China (973 Program; No. 2011CB503803), the National Natural Science Foundation of China (No. 81430090), and Beijing Key Laboratory of Environmental Toxicology (No. 2016HJDL04).
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2023, Environmental PollutionCitation Excerpt :Zhou et al. reported that high dose PM2.5 exposure over a 24-hr period “overwhelmed” repair processes in human bronchial epithelial cells leading to inflammatory responses. Their study showed that lower dose PM2.5 exposure over 10 days allowed for protective cellular responses, preventing the same degree of inflammation induced by the shorter-term high intensity exposure (Zhou et al., 2017). In a high-risk population of adults with cardiac disease, 2-hr, but not 24-or 48-hr, moving mean, of PM2.5 and BC were associated with increased risk of atrial fibrillation, indicating that shorter exposure windows are more relevant to health effects (Link et al., 2013).
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This paper has been recommended for acceptance by Kimberly Hageman.