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Inhibition of human neutrophil leukotriene B4 synthesis in essential fatty acid deficiency: Role of leukotriene a hydrolase

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Lipids

Abstract

A female subject dependent on long-term total parenteral nutrition developed an aversion and noncompliance to a prescribed weekly lipid infusion designed to meet essential fatty acid (EFA) requirements. Fatty acids (FA) in the subject's plasma and isolated peripheral blood neurophils were analyzed in search of biochemical evidence of EFA deficiency. Neutrophil 5-lipoxygenase metabolism was examined to assess the possible effects of EFA deficiency on neutrophil eicosanoid metabolism. EFA deficiency was confirmed by marked depletion of linoleic acid (18∶2n−6) and accumulation of eicosatrienoic acid (ETrA; 20∶3n−9) in plasma and neutrophil phospholipids. In the neutrophils, ETrA comprised 5.2% of phospholipid FA (normal reference values <0.1%), and arachidonic acid (AA; 20∶4n−6) comprised 8.6% of phospholipid FA (normal reference range 10–16%). When stimulated by A23187in vitro on three separate occasions, the subject's neutrophils displayed impaired synthesis of leukotriene B4 (LTB4), but produced normal amounts of 5-hydroxyeicosatetraenoic acid andall-trans isomers of LTB4 formed nonenzymatically from leukotriene A4 (LTA4). This pattern of synthesis suggested inhibition of LTA hydrolase and was also seen in neutrophils from healthy subjects by addition of exogenous ETrAin vitro. Comparative studies of the effects of ETrA and eico-sapentaenoic acid (20∶5n−3) on neutrophilsin vitro suggested that ETrA is the more potent inhibitor. Accumulation of ETrA, rather than depletion of AA, appears principally responsible for the observed impairment of neutrophil LTB4 synthesis seen in this EFA-deficient subject.

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Abbreviations

AA:

arachidonic acid (20∶4n−6)

EFA:

essential fatty acids

EPA:

eicosapentaenoic acid

ETrA:

n−9 eicosatrienoic acid (20∶3n−9)

FA:

fatty acids(s)

HPLC:

high-performance liquid chromatography

LA:

linoleic acide (18∶2n−6)

LTA:

leukotriene A

LTB4 :

leukotriene B4

5-HETE:

5-hydroxyeicosatetraenoic acid

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Authors and Affiliations

  1. Department of Paediatrics, Flinders Medical Centre, Bedford Park, South Australia, Australia

    Mark A. Neumann & Robert A. Gibson

  2. Pheumatology Unit, Royal Adelaide Hospital, North Terrace, 5000, Adelaide, South Australia, Australia

    Leslie G. Cleland, Michael J. James & Susanna M. Proudman

Authors
  1. Leslie G. Cleland
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  2. Michael J. James
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  3. Susanna M. Proudman
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  4. Mark A. Neumann
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  5. Robert A. Gibson
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Cleland, L.G., James, M.J., Proudman, S.M. et al. Inhibition of human neutrophil leukotriene B4 synthesis in essential fatty acid deficiency: Role of leukotriene a hydrolase. Lipids 29, 151–155 (1994). https://doi.org/10.1007/BF02536722

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  • DOI: https://doi.org/10.1007/BF02536722

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