What Is New About Eosinophil Activation in Asthma and Allergic Disease

Abstract

Eosinophils play a critical role in the pathogenesis of allergic diseases such as asthma. Prostaglandin D2 (PGD2), a lipid mediator produced by activated mast cells, and PGD2-derived prostaglandin Js (PGJs) are involved in allergic inflammation. However, PGD2 and PGJs in inflammatory conditions display both pro- and anti-inflammatory effects, hence the functional role of those lipid mediators is still controversial. PGD2 receptors, which are G protein-coupled receptors (GPCRs), the D-prostanoid receptor 1 (DP1) and the chemoattractant receptor-homologous molecule expressed on T-helper-type-2 cells (CRTH2) have been cloned. Furthermore, studies using deficient mouse and receptor-specific antibodies in vitro reveal that CRTH2 and DP1 promote and alleviate inflammation, respectively. Moreover, PGJs exerts its effects not only through DP1 and CRTH2, but also through peroxisome proliferator-activated receptor- (PPAR- ), which negatively regulates inflammation. DP1, CRTH2, and PPAR- are expressed on various inflammatory cells including eosinophils. Thus, these evidences render difficult the understanding of the functional role of PDG2 and its metabolite in allergic response involving eosinophils. Here, we examine the functional role of DP1/CRTH2 and PPAR- on eosinophilic inflammation, and discuss new therapeutic strategies for eosinophil-associated diseases focused on PGD2 and its metabolites.