Modulation of arachidonic and linoleic acid metabolites in myeloperoxidase-deficient mice during acute inflammation
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Modulation of arachidonic and linoleic acid metabolites in myeloperoxidase-deficient mice during acute inflammation. / Kubala, Lukas; Schmelzer, Kara R; Klinke, Anna; Kolarova, Hana; Baldus, Stephan; Hammock, Bruce D; Eiserich, Jason P.
In: FREE RADICAL BIO MED, Vol. 48, No. 10, 15.05.2010, p. 1311-1320.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Modulation of arachidonic and linoleic acid metabolites in myeloperoxidase-deficient mice during acute inflammation
AU - Kubala, Lukas
AU - Schmelzer, Kara R
AU - Klinke, Anna
AU - Kolarova, Hana
AU - Baldus, Stephan
AU - Hammock, Bruce D
AU - Eiserich, Jason P
N1 - Copyright 2010 Elsevier Inc. All rights reserved.
PY - 2010/5/15
Y1 - 2010/5/15
N2 - 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.
AB - 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.
KW - Animals
KW - Arachidonic Acid/metabolism
KW - Chromatography, Liquid
KW - Disease Models, Animal
KW - Epoxy Compounds/blood
KW - Fatty Acids, Unsaturated/blood
KW - Hydroxyeicosatetraenoic Acids/blood
KW - Inflammation
KW - Linoleic Acid/metabolism
KW - Lipopolysaccharides/administration & dosage
KW - Male
KW - Mass Spectrometry
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Neutrophils/metabolism
KW - Peroxidase/genetics
KW - Shock, Septic/blood
U2 - 10.1016/j.freeradbiomed.2010.02.010
DO - 10.1016/j.freeradbiomed.2010.02.010
M3 - SCORING: Journal article
C2 - 20156554
VL - 48
SP - 1311
EP - 1320
JO - FREE RADICAL BIO MED
JF - FREE RADICAL BIO MED
SN - 0891-5849
IS - 10
ER -