R2D(2) for C(4)Eo: an 'alliance' of PGD(2) receptors is required for LTC(4) production by human eosinophils.

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.