Composition of Inhaled Urban Air Particles Determines Acute Pulmonary Responses

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Abstract
Urban particles have a complex heterogeneous composition. To determine which components contribute to the toxicity of inhaled ambient air particles, six different experiments were done using normal Sprague-Dawley rats exposed for 3 consecutive days, for 5 h per day, to either concentrated air particles (CAPs) or filtered air sham conditions (8–12 animals per experimental group per experiment). For each exposure, mass, sulfate, elemental carbon, organic carbon and elemental analysis by X-ray fluorescence were determined. Rotating factor analysis was used to identify component representatives for constituents with the same day-to-day variation. Bronchoalveolar lavage (BAL) was done 24 h after the last exposure on at least six randomly selected animals per group, assessing both cell and fluid parameters. RNA was collected from the lung tissue and BAL cells of each animal, then purified, pooled and hybridized to Affymetrix® rat genome expression microarrays to assess differences in mRNA between the CAPs and sham groups. Significant increases in neutrophils in BAL correlated with measured mass concentrations and particle components associated with urban traffic. Pro-inflammatory mediators/receptors, vascular activation mediators and organic chemical detoxification enzymes all indicated substantial increases in mRNA in CAPs-exposed compared with shamexposed animals. The mRNA detected for immune enhancers and vascular dilatation mediators were substantially decreased with CAPs exposure. Identifying cellular responses and mediators in relation to responsible components in the particles are important steps in understanding the effects of inhaled ambient particles.
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