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National Institute of Environmental Health Sciences

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Publication Detail

Title: Modulation of arachidonic and linoleic acid metabolites in myeloperoxidase-deficient mice during acute inflammation.

Authors: Kubala, Lukas; Schmelzer, Kara R; Klinke, Anna; Kolarova, Hana; Baldus, Stephan; Hammock, Bruce D; Eiserich, Jason P

Published In Free Radic Biol Med, (2010 May 15)

Abstract: Acute inflammation is a common feature of many life-threatening pathologies, including septic shock. One hallmark of acute inflammation is the peroxidation of polyunsaturated fatty acids forming bioactive products that regulate inflammation. Myeloperoxidase (MPO) is an abundant phagocyte-derived hemoprotein released during phagocyte activation. Here, we investigated the role of MPO in modulating biologically active arachidonic acid (AA) and linoleic acid (LA) metabolites during acute inflammation. Wild-type and MPO-knockout (KO) mice were exposed to intraperitoneally injected endotoxin for 24 h, and plasma LA and AA oxidation products were comprehensively analyzed using a liquid chromatography-mass spectrometry method. Compared to wild-type mice, MPO-KO mice had significantly lower plasma levels of LA epoxides and corresponding LA- and AA-derived fatty acid diols. AA and LA hydroxy intermediates (hydroxyeicosatetraenoic and hydroxyoctadecadienoic acids) were also significantly lower in MPO-KO mice. Conversely, MPO-deficient mice had significantly higher plasma levels of cysteinyl-leukotrienes with well-known proinflammatory properties. In vitro experiments revealed significantly lower amounts of AA and LA epoxides, LA- and AA-derived fatty acid diols, and AA and LA hydroxy intermediates in stimulated polymorphonuclear neutrophils isolated from MPO-KO mice. Our results demonstrate that MPO modulates the balance of pro- and anti-inflammatory lipid mediators during acute inflammation and, in this way, may control acute inflammatory diseases.

PubMed ID: 20156554 Exiting the NIEHS site

MeSH Terms: Animals; Arachidonic Acid/metabolism*; Chromatography, Liquid; Disease Models, Animal; Epoxy Compounds/blood; Fatty Acids, Unsaturated/blood; Hydroxyeicosatetraenoic Acids/blood; Inflammation; Linoleic Acid/metabolism*; Lipopolysaccharides/administration & dosage; Male; Mass Spectrometry; Mice; Mice, Inbred C57BL; Mice, Knockout; Neutrophils/metabolism*; Neutrophils/pathology; Peroxidase/genetics*; Shock, Septic/blood; Shock, Septic/metabolism*

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