Pharmacological evidence that the inhibitory effects of prostaglandin E2 are mediated by the EP2 and EP4 receptors in human neutrophils.

Prostaglandin E₂ (PGE₂) is a recognized inhibitor of granulocyte functions. However, most of the data supporting this was obtained when available pharmacological tools mainly targeted the EP₂ receptor. Herein, we revisited the inhibitory effect of PGE₂ on reactive oxygen species production, leukotriene biosynthesis, and migration in human neutrophils. Our data confirm the inhibitory effect of PGE₂ on these functions and unravel that the effect of PGE₂ on human neutrophils is obtained by the combined action of EP₂ and EP₄ agonism. Accordingly, we also demonstrate that the inhibitory effect of PGE₂ is fully prevented only by the combination of EP₂ and EP₄ receptor antagonists, underscoring the importance of targeting both receptors in the effect of PGE₂. Conversely, we also show that the inhibition of ROS production by human eosinophils only involves the EP₄ receptor, despite the fact that they also express the EP₂ receptor. [ABSTRACT FROM AUTHOR]