Lung Function Changes in Mice Sensitized to Ammonium Hexachloroplatinate
Williams, W., J. Lehmann, E. Boykin, M. Selgrade, AND D. Lehmann. Lung Function Changes in Mice Sensitized to Ammonium Hexachloroplatinate. INHALATION TOXICOLOGY. Informa Healthcare USA, New York, NY, 27(10):468-80, (2015).
Occupational exposure to halogenated platinum salts can trigger the development of asthma. The purpose of this work was to mouse model of platinum hypersensitivity with the capacity to assess changes in lung function. This model will be useful for assessing the variable allergenic potential of different platinum compounds, potential for cross-reactivity among platinum compounds, effect of exposure to real-world diesel exhaust containing platinum, and for investigating the possible effects of other fuel additives.
Occupational exposure to halogenated platinum salts can trigger the development of asthma. The risk to the general population that may result from the use of platinum in catalytic converters and its emerging use as a diesel fuel additive is unclear. To investigate pulmonary responses to platinum, we developed a mouse model of platinum hypersensitivity. Mice were sensitized through application of ammonium hexachloroplatinate (AHCP) to the shaved back on days 0, 5 and 19, and to each ear on days 10, 11 and 12. On days 24 and 29, mice were challenged by oropharyngeal aspiration with AHCP in saline. Before and immediately after challenge, pulmonary responses were assessed using whole body plethysmography (WBP). A dose-dependentincrease in immediate responses was observed in AHCP-sensitized and challenged mice. On days 26 and 31, changes in ventilatory responses to methacholine (Mch) aerosol were assessed by WBP; dose-dependent increases in Mch responsiveness occurred in sensitized mice. Lymph node cell counts indicate a proliferative response in lymph nodes drainng the sites of application. Bronchoalveolar lavage fluid harvested from sensitized mice contained an average of 5% eosinophils compared to less than 0.5% in non-sensitized mice (p < 0.05); significant increases in total serum immunoglobulin E were observed for all sensitized mice. Although a second airway challenge on day 29 affected some results, only one airway challenge was needed to observe changes in lung function.
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Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
ENVIRONMENTAL PUBLIC HEALTH DIVISION
CARDIOPULMONARY AND IMMUNOTOXICOLOGY BRANCH