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Am J Reprod Immunol. 2014 Jan;71(1):34-43. doi: 10.1111/aji.12153. Epub 2013 Aug 1.

EP4 and EP2 receptor activation of protein kinase A by prostaglandin E2 impairs macrophage phagocytosis of Clostridium sordellii.

Author information

1
Division of Infectious Diseases, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI, USA.

Abstract

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) E2 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:

PGE2 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 EP2. This was supported by EP receptor expression data and the use of pharmacological receptor antagonists. In addition, the PKA isoform RI appeared to be more important than RII in mediating the suppression of ingestion of C. sordellii.

CONCLUSION:

The endogenous lipid mediator PGE2 impairs human innate immune responses against C. sordellii.

KEYWORDS:

Abortion; endometritis; innate immunity; phagocytosis; pregnancy; toxic shock syndrome

PMID:
23902376
PMCID:
PMC3864121
DOI:
10.1111/aji.12153
[Indexed for MEDLINE]
Free PMC Article

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