R2D 2 for C 4Eo: An 'alliance' of PGD 2 receptors is required for LTC 4 production by human eosinophils

Abstract

Eosinophils play important roles in limiting parasitic infection and in allergic inflammation in the asthmatic airways. Activation of eosinophils by diverse stimuli, including prostaglandin D 2 (PD 2), leads to leukotriene C 4 (LTC 4) synthesis that contributes to the expulsion of parasites and to epithelial injury in allergic inflammation. Mesquita-Santos et al. in this issue of the journal describe a collaboration between the two PGD 2 receptors, DP 1 and DP 2[also known as CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 lymphocytes)] that is required to trigger LTC 4 synthesis. DP 1 receptors coupled to G αs increase adenylate cyclase activity and cAMP/ protein kinase A-dependent formation of lipid bodies, and DP 2 receptors coupled to G αi increase calcium. Each of these signals is required for LTC 4 production. These observations lead to consideration of the effects of other stimuli for eosinophil cAMP, such as the β 2-adrenoceptor agonists, which inhibit rather than enhance LTC 4 production. © 2011 The British Pharmacological Society.