On the relationship between leukotriene and lipoxin production by human neutrophils: evidence for differential metabolism of 15-HETE and 5-HETE

Biochim Biophys Acta. 1989 Aug 8;1004(2):158-68. doi: 10.1016/0005-2760(89)90264-6.


Lipoxygenase (LO) products generated by human PMN were examined utilizing a gradient-HPLC and rapid spectral detector which permitted continuous UV-spectral monitoring of leukotrienes, lipoxins and related oxygenated products of arachidonic acid. When exposed to the ionophore A23187, PMN generated LTB4 and its omega-oxidation products as well as LXA4, LXB4, and 7-cis-11-trans-LXA4 from endogenous sources. Addition of 15-HETE changed the profile of products generated by activated PMN and led to a time- and dose-dependent increase in lipoxins and related compounds while the production of LTB4 and its omega-oxidation products was inhibited. Results of time-course and radiolabel studies revealed that 15-HETE is rapidly transformed within 15 s to 5,15-DHETE and conjugated tetraene-containing products, and that the inhibition of leukotriene formation followed a similar time-course. In contrast, PMN did not generate either lipoxins or related products from 5-[3H]HETE, nor did 5-HETE block leukotriene formation. Stimulated PMN generated 5,15-DHETE from exogenous 5-HETE, while in the absence of ionophore, 5-HETE was transformed to 5,20-HETE. These results indicate that PMN can generate lipoxins and related products from endogenous sources and that 15-HETE and 5-HETE are transformed by different routes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Calcimycin / pharmacology
  • Chromatography, High Pressure Liquid
  • Gas Chromatography-Mass Spectrometry
  • Humans
  • Hydroxyeicosatetraenoic Acids / blood*
  • Hydroxyeicosatetraenoic Acids / pharmacology
  • Kinetics
  • Leukotriene B4 / blood
  • Leukotrienes / blood*
  • Lipoxins*
  • Neutrophils / drug effects
  • Neutrophils / metabolism*
  • Spectrophotometry, Ultraviolet


  • Hydroxyeicosatetraenoic Acids
  • Leukotrienes
  • Lipoxins
  • lipoxin A4
  • Leukotriene B4
  • Calcimycin
  • 5-hydroxy-6,8,11,14-eicosatetraenoic acid
  • 15-hydroxy-5,8,11,13-eicosatetraenoic acid
  • lipoxin B4