Eicosapentaenoic acid modulates arachidonic acid metabolism in rat alveolar macrophages activated by silica.
Eicosapentaenoic acid (EPA) was used to modulate the activation of alveolar macrophages, to examine its potential anti-inflammatory effect in addition to its anti-arteriosclerotic or anti-thrombotic effects. Wistar strain rat alveolar macrophages (2 x 10(6) cell) obtained by bronchoalveolar lavage were preincubated with EPA (0-20 microM), and further incubated with 1 mg of silica for 90 min. Leukotriene (LT) B4 and LTB5 of the supernatant were analyzed by reverse phase HPLC. EPA inhibited the production of LTB4 dose-dependently. The production of LTB5, a metabolite from EPA, was increased at low concentrations of EPA (0-10 microM) and decreased at high concentrations (>10 microM). These results suggest that EPA is competitive with arachidonic acid (AA) at low concentrations, and that EPA may inhibit AA metabolism via inhibition of 5-lipoxygenase or phospholipase A2 at high concentrations.
Saku
N
N
Department of Pulmonary Medicine, Jichi Medical School, Tochigi, Japan.
Kobayashi
J
J
Kitamura
S
S
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002851:Chromatography, High Pressure Liquid; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives / Q000032:analysis / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007975:Leukotriene B4 / Q000031:analogs & derivatives / Q000032:analysis; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects*; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism*; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D051381:Rats; D017208:Rats, Wistar; D012822:Silicon Dioxide / Q000494:pharmacology*
D016859:Lipoxygenase Inhibitors; D007975:Leukotriene B4; D016718:Arachidonic Acid; D012822:Silicon Dioxide; C040212:leukotriene B5; D015118:Eicosapentaenoic Acid; D007770:L-Lactate Dehydrogenase; D001094:Arachidonate 5-Lipoxygenase; D010741:Phospholipases A; D054467:Phospholipases A2