EP4 and EP2 Receptor Activation of Protein Kinase A by Prostaglandin E 2 Impairs Macrophage Phagocytosis of Clostridium sordellii

Problem Clostridium sordellii causes endometrial infections, but little is known regarding host defenses against this pathogen. Method of study We tested the hypothesis that the immunoregulatory lipid prostaglandin ( PG ) E 2 suppresses human macrophage clearance of C . sordellii through receptor‐induced increases in intracellular cyclic adenosine monophosphate ( cAMP ). The THP ‐1 macrophage cell line was used to quantify C. sordellii phagocytosis. Results PGE 2 increased cAMP levels, activated protein kinase A ( PKA ), and inhibited the class A scavenger receptor‐dependent phagocytosis of C. sordellii . Activation of the EP2 and EP4 receptors increased intracellular cAMP and inhibited phagocytosis, with evidence favoring a more important role for EP4 over EP 2. This was supported by EP receptor expression data and the use of pharmacological receptor antagonists. In addition, the PKA isoform R I appeared to be more important than R II in mediating the suppression of ingestion of C. sordellii . Conclusion The endogenous lipid mediator PGE 2 impairs human innate immune responses against C. sordellii .