LTA(4)-derived 5-oxo-eicosatetraenoic acid: pH-dependent formation and interaction with the LTB(4) receptor of human polymorphonuclear leukocytes

Biochim Biophys Acta. 2000 Feb 24;1484(1):51-8. doi: 10.1016/s1388-1981(99)00198-5.


5-oxo-(7E,9E,11Z,14Z)-eicosatetraenoic acid (5-oxo-ETE) has been identified as a non-enzymatic hydrolysis product of leukotriene A(4) (LTA(4)) in addition to 5,12-dihydroxy-(6E,8E,10E, 14Z)-eicosatetraenoic acids (5,12-diHETEs) and 5,6-dihydroxy-(7E,9E, 11Z,14Z)-eicosatetraenoic acids (5,6-diHETEs). The amount of 5-oxo-ETE detected in the mixture of the hydrolysis products of LTA(4) was found to be pH-dependent. After incubation of LTA(4) in aqueous medium, the ratio of 5-oxo-ETE to 5,12-diHETE was 1:6 at pH 7.5, and 1:1 at pH 9.5. 5-Oxo-ETE was isolated from the alkaline hydrolysis products of LTA(4) in order to evaluate its effects on human polymorphonuclear (PMN) leukocytes. 5-Oxo-ETE induced a rapid and dose-dependent mobilization of calcium in PMN leukocytes with an EC(50) of 250 nM, as compared to values of 3.5 nM for leukotriene B(4) (LTB(4)500 nM for 5(S)-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoic acid (5-HETE). Pretreatment of the cells with LTB(4) totally abolished the calcium response induced by 5-oxo-ETE. In contrast, the preincubation with 5-oxo-ETE did not affect the calcium mobilization induced by LTB(4). The calcium response induced by 5-oxo-ETE was totally inhibited by the specific LTB(4) receptor antagonist LY223982. These data demonstrate that 5-oxo-ETE can induce calcium mobilization in PMN leukocyte via the LTB(4) receptor in contrast to the closely related analog 5-oxo-(6E,8Z,11Z, 14Z)-eicosatetraenoic acid which is known to activate human neutrophils by a mechanism independent of the receptor for LTB(4).

MeSH terms

  • Arachidonic Acids / chemical synthesis
  • Arachidonic Acids / metabolism*
  • Arachidonic Acids / pharmacology
  • Benzophenones / pharmacology
  • Calcium / metabolism
  • Fura-2
  • Humans
  • Hydrogen-Ion Concentration
  • Leukotriene A4 / chemistry
  • Leukotriene Antagonists / pharmacology
  • Neutrophils / drug effects
  • Neutrophils / metabolism*
  • Receptors, Leukotriene B4 / metabolism*


  • Arachidonic Acids
  • Benzophenones
  • Leukotriene A4
  • Leukotriene Antagonists
  • Receptors, Leukotriene B4
  • LY 223982
  • 5-oxo-6,8,11,14-eicosatetraenoic acid
  • Calcium
  • Fura-2