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

Free Radic Biol Med. 2010 May 15;48(10):1311-20. doi: 10.1016/j.freeradbiomed.2010.02.010. Epub 2010 Feb 13.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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*


  • Epoxy Compounds
  • Fatty Acids, Unsaturated
  • Hydroxyeicosatetraenoic Acids
  • Lipopolysaccharides
  • hydroxyoctadecadienoic acid
  • Arachidonic Acid
  • Linoleic Acid
  • Peroxidase