Original ContributionModulation of arachidonic and linoleic acid metabolites in myeloperoxidase-deficient mice during acute inflammation
Section snippets
Materials
The following AA and LA metabolites were purchased from Cayman Chemicals (Ann Arbor, MI, USA): (±)9(10)-epoxy-12Z-octadecenoic acid [9(10)-EpOME], (±)12(13)-epoxy-9Z-octadecenoic acid [12(13)-EpOME], (±)5(6)-epoxy-8Z,11Z,14Z-eicosatrienoic acid [5(6)-EET)], (±)8(9)-epoxy-5Z,11Z,14Z-eicosatrienoic acid [8(9)-EET], (±)14(15)-epoxy-5Z,8Z,11Z-eicosatrienoic acid [14(15)-EET], (±)11(12)-epoxy-5Z,8Z,14Z-eicosatrienoic acid [11(12)-EET], (±)13-hydroxy-9Z,11E-octadecadienoic acid (13-HODE),
MPO deficiency suppresses endotoxemia-induced formation of LA epoxides and vicinal dihydroxy metabolites of AA and LA
To model acute inflammation associated with systemic endotoxemia/sepsis, we injected mice ip with LPS and measured AA and LA metabolites 24 h later. In wild-type animals, LPS-induced endotoxemia greatly increased the plasma levels of LA epoxides (EpOMEs) as well as vicinal dihydroxy metabolites of AA and LA (DHETEs and DHOMEs, respectively), confirming that the P450-epoxygenase/soluble epoxide hydrolase lipid metabolism pathways are activated in our noninfectious model of systemic sepsis (Table
Discussion
Our results illustrate the significance of MPO in the formation of biologically active metabolites of AA and LA. Data suggest that during acute inflammation, MPO plays an important role in the formation of AA and LA epoxides and hydroxy intermediates together with the catabolism of cysteinyl-LTs. Accordingly, the formation of AA and LA lipid mediators (HETEs, HODEs, and H(P)ODEs) was suppressed in MPO-KO mice and PMNs isolated from these animals. Interestingly, the difference between AA and LA
Acknowledgments
This work was supported by a postdoctoral fellowship from Philip Morris USA, Inc., and Philip Morris International (to L.K.); grants from The Academy of Sciences of the Czech Republic, M200040908, AV0Z50040507, and AV0Z50040702 (to L.K.); a University of California at Davis Health Systems Research Award (to J.P.E.); and the Paul F. Gulyassy Endowed Professorship (to J.P.E.). K.S. received the John Kinsella Dissertation Award and was supported by an NIEHS Training Grant in Environmental
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