R2D2 for C4Eo: an ‘alliance’ of PGD2 receptors is required for LTC4 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 D2 (PD2), leads to leukotriene C4 (LTC4) 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 PGD2 receptors, DP1 and DP2[also known as CRTH2 (chemoattractant receptor‐homologous molecule expressed on Th2 lymphocytes)] that is required to trigger LTC4 synthesis. DP1 receptors coupled to Gαs increase adenylate cyclase activity and cAMP/ protein kinase A–dependent formation of lipid bodies, and DP2 receptors coupled to Gαi increase calcium. Each of these signals is required for LTC4 production. These observations lead to consideration of the effects of other stimuli for eosinophil cAMP, such as the β2‐adrenoceptor agonists, which inhibit rather than enhance LTC4 production.LINKED ARTICLE This article is a commentary on Mesquita‐Santos et al., pp. 1674–1685 of this issue. To view this paper visit http://dx.doi.org/10.1111/j.1476‐5381.2010.01086.x