Pharmacologic Regulation of Eosinophil Activation: New Therapeutic Targets

摘要

Eosinophils are associated to various allergic diseases, in particular asthma and atopic dermatitis [1]. In order to investigate new potential therapeutic targets, which would suppress eosino-philia and/or eosinophil function, we examined the role of prostaglandin (PG) D2 and peroxisome proliferalor-activated receptors (PPAR) in the regulation of eosinophilia in mouse models of allergen-induced asthma and atopic dermatitis (AD). Mast cells also indirectly participate in asthmatic reactions and potentiate AD [2, 3]. Indeed, upon activation by IgE and multi valent Ag, mast cells release several inflammatory mediators such as histamine, proteases, cytokines, and eicosanoids, including leuko-trienes and PGs [4]. Among the latter, PGD2 is the most abundantly produced. During acute asthmatic episodes, PGD_2 is released by mast cells into the lungs and causes bronchoconstriction. PGD_2, as well as histamine, directly activates eosinophils, promotes their recruitment and affects other key parameters of lung inflammation, in particular vascular permeability.