Cross-reactivity between halogenated platinum salts in an immediate-type respiratory hypersensitivity model

Abstract

Halogenated platinum salts can trigger the development of occupational asthma. Until recently, laboratory research into the development and manifestation of platinum hypersensitivity responses were hindered by the lack of an animal model suitable for assessing the functional consequences of allergic sensitization. We employed a newly developed mouse model to assess the potential allergenicity of ammonium tetrachloroplatinate (ATCP), compare the relative potency of ATCP and another platinum salt, ammonium hexachloroplatinate (AHCP) and assess potential cross-reactivity. Mice were topically sensitized with ATCP before being challenged by intratracheal aspiration (IA) with ATCP. Ventilatory responses were assessed using whole-body plethysmography (WBP). An immediate response (IR) was observed in ATCP-sensitized and challenged mice. Two days later, responsiveness to the nonspecific stimuli methacholine (Mch) was detected in ATCP-sensitized mice using WBP. Bronchoalveolar lavage fluid collected from sensitized mice contained an average of 3.3% eosinophils compared to less than 0.5% in non-sensitized mice (p<.05). Serum harvested from sensitized mice also contained increased total serum immunoglobulin E (p<.05). These data are the first to demonstrate that topical exposure to ATCP is sufficient to develop immediate type hypersensitivity and that a single intra-airway challenge is capable of triggering pulmonary responses. To investigate potential cross-reactivity, mice were sensitized to AHCP and, challenged by a single IA with a second platinum compound, ATCP. Compared to non-sensitized mice challenged with ATCP, these mice exhibited an IR, responsiveness to Mch, and eosinophilic infiltration in the lungs similar to that achieved with AHCP challenge, thus demonstrating cross-reactivity.

Keywords:

• Platinum
• ammonium hexachloroplatinate
• ammonium tetrachloroplatinate
• occupational asthma
• respiratory hypersensitivity
• cross-reactivity
• whole-body plethysmography
• pulmonary hyperresponsiveness

Acknowledgements

The authors thank C. Copeland, L. Copeland, D. Andrews and J. Richards for their expert technical assistance. We also thank Drs. MJ. Selgrade, A. Farraj and I. Gilmour for their thoughtful and critical review of this work.

Disclosure statement

This article has been reviewed by the U.S. Environmental Protection Agency and approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the Agency or of the US Federal Government, nor does the mention of trade names or commercial products constitute endorsement or recommendations for use of those products. The authors report no financial or other conflicts of interest. The authors alone are responsible for the content and writing of this article.