Prostaglandin D2 is a potent chemoattractant for human eosinophils that acts via a novel DIP receptor

Prostaglandin D-2 (PGD(2)) is released following exposure of asthmatics to allergen and acts via the adenylyl cyclase-coupled receptor for PGD(2) (DID receptor). In this study, it is reported that human eosinophils possess this receptor, which would be expected to inhibit their activation. In contrast, it was found that prostaglandin D-2 is a potent stimulator of eosinophil chemotaxis, actin polymerization, CD11b expression, and L-selectin shedding. These responses are specific for eosinophils, as neutrophils display little or no response to prostaglandin D-2 They were not due to interaction with receptors for other prostanoids, as prostaglandins E-2 and F-2 alpha, U46619 (a thromboxane A(2) analogue), and carbaprostacyclin (a prostacyclin analogue) displayed little or no activity. Furthermore, they were not shared by the selective DID receptor agonist BW245C and were not prevented by the selective DID receptor antagonist BWA868C, indicating that they were not mediated by DID receptors. In contrast, the prostaglandin D2 metabolite 13,14-dihydro-15-oxoprostaglandin D-2 induced eosinophil activation but did not stimulate DID receptor-mediated adenosine 3 ' ,5 ' -cyclic monophosphate (cAMP) formation. These results indicate that in addition to the classic inhibitory DID, receptor, eosinophils possess a second, novel DP2 receptor that is associated with PGD(2)-induced cell activation. These 2 receptors appear to interact to regulate eosinophil responses to PGD(2), as blockade of DPI receptor-mediated cAMP production by BWA868C resulted in enhanced DP2 receptor-mediated stimulation of CD11b expression. The balance between DPI and DP2 receptors could determine the degree to which prostaglandin D-2 can activate eosinophils and may play a role in eosinophil recruitment in asthma.