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AN ANIMAL MODEL OF PLATINUM (PT) HYPERSENSITIVITY
Citation:
BOYKIN, E., J. R. LEHMANN, D. L. DOERFLER, S. H. GAVETT, AND M. K. SELGRADE. AN ANIMAL MODEL OF PLATINUM (PT) HYPERSENSITIVITY. Presented at Society of Toxicology Annual Meeting, Seattle, WA, March 16 - 20, 2008.
Impact/Purpose:
We describe here a mouse model of Pt sensitization that may be useful for studying risks associated with Pt allergy.
Description:
Exposure to Pt salts has been associated with occupational asthma. Pt, the most active component and widely used metal in catalytic converters, is released in automobile exhaust and is a proposed diesel fuel additive. Thus, with the potential for widespread environmental distribution, the risk for asthma in the general population is a concern. We describe here a mouse model of Pt sensitization that may be useful for studying risks associated with Pt allergy. Mice were sensitized dermally with 100 µl 1% ammonium hexachloroplatinate (AHCP) in DMSO to the shaved back on days 0, 5 and 19, and 25 µl to each ear on days 10, 11 and 12. Unsensitized mice received vehicle. On day 24, sensitized mice were challenged intranasally (i.n.) with 0, 1, 3, 10 or 30 µg AHCP in saline with or without 50 µg of diesel exhaust particles (DEP). Unsensitized mice were challenged i.n. with 0 or 30 µg AHCP with or without DEP. Airway responses were assessed by whole body plethysmography (WBP) before and immediately after i.n. dosing. On day 26 reactivity to methacholine aerosol was assessed by WBP. Mice were then sacrificed and serum and bronchoalveolar lavage fluid (BAL) collected. A significant increase in total serum IgE occurred in all sensitized mice. A dose dependent increase in immediate airway responses (IAR) was observed in AHCP sensitized and challenged mice. Unsensitized mice challenged with 30 µg AHCP had an increased IAR relative to vehicle mice, but significantly lower than sensitized mice challenged with 30 µg AHCP. Modest dose dependent increases in MCH responsiveness occurred, but without corresponding changes in BAL cell influx. Exposure to DEP had no effect on any parameters. The data show that mice sensitized to Pt salts via the dermal route respond to respiratory exposures. This model may be useful for assessing cross reactivity between different forms of Pt salts, further exploration of adjuvant effects of DEP, developing dose responses, and screening of DEP derived from burning fuels with Pt additives. (This abstract does not reflect EPA policy).