Linoleic acid and dihomogammalinolenic acid inhibit leukotriene B4 formation and stimulate the formation of their 15-lipoxygenase products by human neutrophils in vitro. Evidence of formation of antiinflammatory compounds

Agents Actions. 1991 Jul;33(3-4):286-91. doi: 10.1007/BF01986575.

Abstract

Enzymatic transformation of the n-6 polyunsaturated fatty acid (PUFA) arachidonic acid (AA) by the 5-lipoxygenase (LO) enzyme results in the formation of leukotrienes (LTs) including leukotriene B4 (LTB4), which is a potent mediator of inflammation. The purpose of the present study was to determine the effect of other n-6 fatty acids on the formation of LTB4 by human neutrophils and to determine if these n-6 fatty acids themselves may be transformed into products with antiinflammatory capacity. Purified neutrophils isolated from heparinized human venous blood were incubated with A23187 (5 microM) and different concentrations (0-100 microM) of the n-6 fatty acids linoleic acid (LA) and dihomo-gamma-linolenic acid (DGLA). LO products were determined by use of quantitative reversed-phase high performance liquid chromatography (RP-HPLC) and mass spectrometry. The formation of LTB4 was dose dependently inhibited by both LA (IC50 = 45 microM) and DGLA (IC50 = 40 microM). This inhibition of LTB4 formation was associated with a dose dependent increase in the formation of the respective 15-LO products of LA (13-hydroxy-octadecadienoic acid; 13-HODE) and DGLA (15-hydroxy-eicosatrienoic acid; 15-HETrE). To determine whether these 15-LO products themselves might inhibit LTB4 formation, neutrophils were incubated with 13-HODE and 15-HETrE. Both 15-LO products lead to a dose-dependent inhibition of LTB4 formation (IC50 = 7.5 microM and IC50 = 0.2 microM). For comparison the 15-LO product of AA, 15-hydroxy-eicosatetraenoic acid (15-HETE), also inhibited LTB4 formation (IC50 = 0.75 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH terms

  • 8,11,14-Eicosatrienoic Acid / pharmacology*
  • Anti-Inflammatory Agents, Non-Steroidal / metabolism*
  • Arachidonate 15-Lipoxygenase / metabolism*
  • Chromatography, High Pressure Liquid
  • Humans
  • Hydroxyeicosatetraenoic Acids / biosynthesis
  • In Vitro Techniques
  • L-Lactate Dehydrogenase / metabolism
  • Leukotriene B4 / biosynthesis*
  • Linoleic Acid
  • Linoleic Acids / biosynthesis
  • Linoleic Acids / pharmacology*
  • Mass Spectrometry
  • Neutrophils / drug effects
  • Neutrophils / enzymology
  • Neutrophils / metabolism*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Hydroxyeicosatetraenoic Acids
  • Linoleic Acids
  • Leukotriene B4
  • 13-hydroxy-9,11-octadecadienoic acid
  • 15-hydroxy-5,8,11,13-eicosatetraenoic acid
  • Linoleic Acid
  • L-Lactate Dehydrogenase
  • Arachidonate 15-Lipoxygenase
  • 8,11,14-Eicosatrienoic Acid