Mast cell mediators cause the early allergic bronchoconstriction in guinea pigs in vivo: a model of relevance to asthma

One feature of allergic asthma, the early allergic reaction (EAR), is not present in the commonly used mouse models. We therefore investigated the mediators involved in EAR in a guinea pig in vivo model of allergic airway inflammation. Animals were sensitized using a single ovalbumin (OVA)/alum injection and challenged with aerosolized OVA on day 14. On day 15, airway resistance was assessed after challenge with OVA or methacholine using the forced oscillation technique, and lung tissue was prepared for histology. The contribution of mast cell mediators was investigated using inhibitors of the main mast cell mediators (histamine [pyrilamine] and cysteinyl-leukotrienes [montelukast] and prostanoids [indomethacin]). OVA-sensitized and challenged animals demonstrated airway hyperresponsiveness to methacholine, and lung tissue eosinophilic inflammation. Antigen challenge induced a strong EAR in the sensitized animals. Treatment with a single compound, or indomethacin together with pyrilamine or montelukast, did not reduce the antigen-induced airway resistance. In contrast, dual treatment with pyrilamine together with montelukast, or triple inhibitor treatment, attenuated approximately 70% of the EAR. We conclude that, as in humans, the guinea pig allergic inflammation model exhibit both EAR and airway hyperresponsiveness, supporting its suitability for in vivo identification of mast cell mediators that contribute to the development of asthma. Moreover, the known mast cell mediato...
Source: Clinical Science - Category: Biomedical Science Authors: Source Type: research