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

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

Research output: Contribution to journalArticle

23 Scopus citations

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 24h, 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.

Original languageEnglish (US)
Pages (from-to)1311-1320
Number of pages10
JournalFree Radical Biology and Medicine
Volume48
Issue number10
DOIs
StatePublished - May 2010

Keywords

  • Epoxygenase
  • Free radicals
  • Lipoxygenase
  • Myeloperoxidase
  • Proinflammatory mediators
  • Sepsis

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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    Kubala, L., Schmelzer, K. R., Klinke, A., Kolarova, H., Baldus, S., Hammock, B. D., & Eiserich, J. P. (2010). Modulation of arachidonic and linoleic acid metabolites in myeloperoxidase-deficient mice during acute inflammation. Free Radical Biology and Medicine, 48(10), 1311-1320. https://doi.org/10.1016/j.freeradbiomed.2010.02.010