Ability of 15-hydroxyeicosatrienoic acid (15-OH-20: 3) to modulate macrophage arachidonic acid metabolism

Robert S. Chapkin, Craig C. Miller, Scott D. Somers, Kent L Erickson

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Mouse peritoneal macrophages metabolize dihomogammalinolenic acid (20:3n-6) primarily to 15-hydroxy-8,11,13-eicosatrienoic acid (15-OH-20:3). Since the biological properties of this novel trienoic eicosanoid remain poorly defined, the effects of increasing concentrations of 15-OH-20:3 and its arachidonic acid (20:4n-6) derived analogue, 15-hydroxy-5,8,11,13-eicosatetraenoic acid (15-HETE), on mouse macrophage 20:4n-6 metabolism were investigated. Resident peritoneal macrophages were prelabeled with [3H]-20:4n-6 and subsequently stimulated with zymosan in the presence of either 15-OH-20:3 or 15-HETE (1-30 μM). After 1 hr, the radiolabeled soluble metabolites were analyzed by reverse phase high performance liquid chromatography. 15-OH-20:3 inhibited zymosan-induced leukotriene C4 (IC50 = 2.4 μM) and 5-HETE (IC50 = 3.1 μM) synthesis. In contrast to the inhibition of macrophage 5-lipoxygenase, 15-OH-20:3 enhanced 12-HETE synthesis (5-30 μM) and had no measurable effect on cyclooxygenase metabolism (1-10 μM) i.e., 6-keto-prostaglandin F1 alpha and prostaglandin E2 synthesis. Addition of exogenous 15-HETE produced similar effects. These results suggest that the manipulation of macrophage 15-OH-20:3n-6 levels may provide a measure of cellular control over 20:4n-6 metabolism, specifically, leukotriene production.

Original languageEnglish (US)
Pages (from-to)799-804
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume153
Issue number2
DOIs
StatePublished - Jun 16 1988

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Macrophages
Arachidonic Acid
Metabolism
Zymosan
Peritoneal Macrophages
Inhibitory Concentration 50
8,11,14-Eicosatrienoic Acid
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
Arachidonate 5-Lipoxygenase
Leukotriene C4
Cyclooxygenase 1
Eicosanoids
Leukotrienes
High performance liquid chromatography
Reverse-Phase Chromatography
Prostaglandin-Endoperoxide Synthases
Metabolites
Dinoprostone
15-hydroxyeicosatrienoic acid
hydroxide ion

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Ability of 15-hydroxyeicosatrienoic acid (15-OH-20 : 3) to modulate macrophage arachidonic acid metabolism. / Chapkin, Robert S.; Miller, Craig C.; Somers, Scott D.; Erickson, Kent L.

In: Biochemical and Biophysical Research Communications, Vol. 153, No. 2, 16.06.1988, p. 799-804.

Research output: Contribution to journalArticle

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