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

Link:
Autor/in:
Erscheinungsjahr:
2010
Medientyp:
Text
Schlagworte:
  • Peroxidase
  • Hypochlorous Acid
  • MPO levels
  • Neutrophils
  • NADPH Oxidase
  • Reactive Oxygen Species
  • Peroxidase
  • Hypochlorous Acid
  • MPO levels
  • Neutrophils
  • NADPH Oxidase
  • Reactive Oxygen Species
  • Epoxy Compounds/blood
  • Neutrophils/metabolism
  • Mice, Inbred C57BL
  • Linoleic Acid/metabolism
  • Male
  • Inflammation
  • Fatty Acids, Unsaturated/blood
  • Mice, Knockout
  • Arachidonic Acid/metabolism
  • Lipopolysaccharides/administration & dosage
  • Animals
  • Mass Spectrometry
  • Chromatography, Liquid
  • Peroxidase/genetics
  • Mice
  • Shock, Septic/blood
  • Disease Models, Animal
  • Hydroxyeicosatetraenoic Acids/blood
Beschreibung:
  • 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. © 2010 Elsevier Inc.
Lizenz:
  • info:eu-repo/semantics/restrictedAccess
Quellsystem:
Forschungsinformationssystem der UHH
Interne Metadaten
Quelldatensatz
oai:www.edit.fis.uni-hamburg.de:publications/06026474-389b-4550-a8b6-f2ca7413efda