Animal models for protein respiratory sensitizers

Abstract

Protein induced respiratory hypersensitivity, particularly atopic disease in general, and allergic asthma in particular, has increased dramatically over the last several decades in the US and other industrialized nations as a result of ill-defined changes in living conditions in modern western society. In addition, work-related asthma has become the most frequently diagnosed occupational respiratory illness. Animal models have demonstrated great utility in developing an understanding of the etiology and mechanisms of many diseases. A few models been developed as predictive models to identify a protein as an allergen or to characterize its potency. Here we describe animal models that have been used to investigate and identify protein respiratory sensitizers. In addition to prototypical experimental design, methods for exposure route, sample collection, and endpoint assessment are described. Some of the most relevant endpoints in assessing the potential for a given protein to induce atopic or allergic asthma respiratory hypersensitivity are the development of cytotropic antibodies (IgE, IgG1), eosinophil influx into the lung, and airway hyperresponsiveness to the sensitizing protein and/or to non-antigenic stimuli (Mch). The utility of technologies such as PCR and multiplexing assay systems is also described. These models and methods have been used to elucidate the potential for protein sources to induce allergy, identify environmental conditions (pollutants) to impact allergy responsiveness, and establish safe exposure limits. As an example, data are presented from an experiment designed to compare the allergenicity of a fungal biopesticide Metarhizium anisopliae (MACA) crude extract with the one of its components, conidia (CON) extract.