Cytotoxic and proinflammatory effects of ambient and source-related particulate matter (PM) in relation to the production of reactive oxygen species (ROS) and cytokine adsorption by particles

Abstract

The composition of airborne particulate matter (PM) varies widely depending on its source, and recent studies have suggested that particle-associated adverse health effects are related to particle composition. The objective of this study was to compare the biological/toxicological effects of different source-related PM. Specifically, we investigated the biological/toxicological effects of standard reference materials (SRMs): non-ferrous dust (PD-1, industrial), urban PM (UPM, SRM1648a), and diesel PM (DPM, SRM2975), and ambient PM_2.5 (PM with an aerodynamic diameter <2.5 µm) collected at an urban site (Toronto, Canada). The dithiothreitol assay was used to measure the redox activity of the particles. Human alveolar epithelial cells (A549) were exposed to a range of concentrations (10–1000 µg/ml) of total PM, and the respective water-soluble and insoluble fractions, for 24 h. Biological responses were then evaluated in terms of cytotoxicity and interleukin (IL)-8 release, and compared with the PM composition and redox activity. We demonstrated that transition metal-enriched PD-1 exhibited the greatest cytotoxic effect (LD₅₀ values of 100–400 µg/ml vs. >1000 µg/ml for the SRM1648a, SRM2975, and ambient PM_2.5). Similarly, the PM-induced release of IL-8 was greatest for PD-1 (~6–9 ng/ml vs. ~1.5–3 ng/ml for others). These endpoints were more responsive to metals as compared with compared with secondary inorganic ions and organic compounds. Interestingly, we demonstrated a high degree of adsorption of IL-8 to the various SRMs and ambient PM_2.5, and subsequently derived a new correction method to aid in interpretation of these data. These characteristics likely impart differential effects toward the toxic and immune effects of PM.

Keywords::

• Particulate matter
• biological/toxicological effects
• standard reference materials
• PM_2.5
• oxidative stress
• inflammation
• cytotoxicity
• chemical composition
• redox activity
• IL-8 adsorption

Acknowledgements

The A549 human alveolar epithelial cell line was kindly provided by Dr. Chung-Wai Chow, Department of Medicine, University of Toronto, Toronto, Canada.

Declaration of interest

Operational funding was provided by Natural Sciences and Engineering Research Council of Canada (NSERC) and Canadian Institutes of Health Research (CIHR) through the Collaborative Health Research Projects (CHRP), and the AllerGen Network of Centres of Excellence (07-A5). Infrastructure of Southern Ontario Centre for Atmospheric Aerosol Research (SOCAAR) was funded by the Canada Foundation for Innovation (CFI) and the Ontario Research Fund (ORF).