Prostaglandin E2 Inhibits the Ability of Neutrophils to Kill Listeria monocytogenes

Abstract

PGE 2 is a lipid-signaling molecule with complex roles in both homeostasis and inflammation. Depending on the cellular context, PGE 2 may also suppress certain immune responses. In this study, we tested whether PGE 2 could inhibit bacterial killing by polymorphonuclear neutrophils (PMN) using a mouse model of foodborne listeriosis. We found that PGE 2 pretreatment decreased the ability of PMN harvested from the bone marrow of either BALB/cByJ or C57BL/6J mice to kill Listeria monocytogenes in vitro. PGE 2 treatment slowed the migration of PMN toward the chemoattractant leukotriene B4, decreased uptake of L. monocytogenes by PMN, and inhibited the respiratory burst of PMN compared with vehicle-treated cells. When immune cells were isolated from the livers of infected mice and tested directly ex vivo for the presence of PGE 2 , BALB/cByJ cells produced significantly more than C57BL/6J cells. Together, these data suggest that robust PGE 2 production can suppress PMN effector functions, leading to decreased bacterial killing, which may contribute to the innate susceptibility of BALB/cByJ mice to infection with the facultative intracellular bacterial pathogen L. monocytogenes.

Oxylipin metabolism is controlled by mitochondrial β-oxidation during bacterial inflammation

“…Next, to address whether macrophage mitochondrial β-oxidation impacts wider oxylipin signaling between other cell types, human phagocyte and T-cell responses to these lipids were determined. Neutrophils were chosen since they are known to be sensitive to PGE 2 , via EP receptor signaling 47 , 48 , while T cells can be regulated by PPARγ, a transcription factor that is regulated by many LOX-derived oxylipins 49 – 55 . Here, reactive oxygen species (ROS) production elicited by Staphylococcus epidermidis , a common pathogen in human peritonitis was measured by aminophenyl fluorescein (APF) fluorescence of whole blood leukocytes 56 .…”

Oxylipin metabolism is controlled by mitochondrial β-oxidation during bacterial inflammation

“…Next, to address whether macrophage mitochondrial β-oxidation impacts wider oxylipin signaling between other cell types, human phagocyte and T cell responses to these lipids were determined. Neutrophils were chosen since they are known to be sensitive to PGE 2 , via EP receptor signaling [47, 48], while T cells can be regulated by PPARγ, a transcription factor that is regulated by many LOX derived oxylipins [49–55]. Here, reactive oxygen species (ROS) production elicited by S. epidermidis , a common pathogen in human peritonitis was measured by aminophenyl fluorescein (APF) fluorescence of whole blood leukocytes [56].…”

Untapped Potential: Therapeutically Targeting Eicosanoids and Endocannabinoids in the Lung

“…Interestingly, PGE2 can also promote proresolving functions. Neutrophils stimulated with PGE2 have reduced reactive oxygen species formation, 21 reduced adhesion to endothelial cells, and reduced chemotaxis 22 …”

“…20 Interestingly, PGE2 can also promote proresolving functions. Neutrophils stimulated with PGE2 have reduced reactive oxygen species formation, 21 reduced adhesion to endothelial cells, and reduced chemotaxis. 22 The action of PGE2 depends on which G protein-coupled transmembrane receptor to which the prostaglandin binds (EP 1 , EP 2 , EP 3 , EP 4 ).…”