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.

Akhtar US, McWhinney RD, Rastogi N, Abbatt JP, Evans GJ, Scott JA.
Inhal Toxicol. 2010 Dec;22 Suppl 2:37-47.

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 (LD(50) 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.

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