Kainate receptor deficient mast cells exhibit increased activation in vivo and in vitro.

Abstract

Abstract Allergies and asthma are common ailments that are on the rise around the world, especially in young children. Mast cells play a direct role in the signs and symptoms characteristic in allergic patients. Kainate is an ionotropic member of the glutamate receptor family and is mainly studied in the brain. Recent investigations, however, have shown the presence of the Kainate Receptor (KAR) in peripheral tissues, including cells of the immune system. Our lab has previously studied the effects of KAR deficient mice and have found that these mice have reduced Th2 responses in a house dust mite extract model of allergic airway inflammation. We sought to determine if KAR deficient mast cells played a role in the phenotype observed. Paradoxically, these mast cells exhibited increased, rather than decreased mediator release in vitro by antigen–dependent degranulation. In vivo, KAR KO mice release significantly more histamine during a model of passive systemic anaphylaxis. Finally, KAR KO mice exhibit an exacerbated temperature drop in response to administered histamine. These results stand in contrast to the inhibition of the asthma model, but indicate that KAR agonist, rather than antagonist treatment of mast cells would be a treatment modality to decrease mast cell activation. Such studies are currently underway.