Mouse Model of Halogenated Platinum Salt Hypersensitivity
Citation:
Williams, W., E. Boykin, C. Copeland, L. Copeland, S. Quell, S. Gavett, M. Selgrade, AND D. Lehmann. Mouse Model of Halogenated Platinum Salt Hypersensitivity. Presented at Society of Toxicology, March 10 - 14, 2013.
Impact/Purpose:
This work is dedicated to developing a mouse model of platinum hypersensitivity. The model will be used to assess the relative sensitizing potency and cross-reactivity between different halogenated Pt salts and for investigating the possible adjuvant effects of diesel exhaust particles.
Description:
Occupational exposure to halogenated platinum salts can trigger the development of asthma. Concern for increased asthma risk exists for the general population due to the use of platinum (Pt) in catalytic converters and its emerging use as a diesel fuel additive. To investigate airway responses to Pt, we developed a mouse model of Pt hypersensitivity. Previously, we confirmed the dermal sensitizing potency of ammonium hexachloroplatinate (AHCP) using an ex vivo [3H]methyl thymidine labeling version of the local lymph node assay in BALB/c mice. Here, we investigated the ability of AHCP to induce airway responses in mice sensitized by the dermal route. Mice were sensitized through application of 100 µL 1% 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, mice were challenged by oropharyngeal aspiration (OPA) with 0 or 100 µg AHCP in saline. Before and immediately after challenge, airway responses were assessed using whole body plethysmography (WBP). On day 26, changes in ventilatory responses to methacholine (Mch) aerosol were assessed by WBP; dose-dependent increases in Mch responsiveness occurred in sensitized mice. Bronchoalveolar lavage fluid harvested from sensitized mice contained an average of 7.5% eosinophils compared to less than 0.5% in control mice (p < 0.05). This model will be useful for assessing both relative sensitizing potency and cross-reactivity between different halogenated Pt salts and for investigating the possible adjuvant effects of diesel exhaust particles. This abstract does not represent EPA policy.