Journal of Lipid Research, Vol 31, 1831-1838, Copyright © 1990 by Lipid Research, Inc.
Catabolism of leukotriene B5 in humans
C von Schacky, C Fahrer and S Fischer
Medizinische Klinik Innenstadt, University of Munich, FRG.
Human neutrophils, enriched by dietary supplementation with
eicosapentaenoic acid, form leukotriene (LT)B5 in addition to LTB4 upon
stimulation. LTB5 is one order of magnitude less biologically active than
the potent chemokinetic and chemoattractant LTB4. Catabolites of LTB5 have
not yet been characterized in vitro and ex vivo. It is unknown whether
catabolism of LTB5 interferes with catabolism of LTB4. This report
describes catabolism of LTB5 to 20-OH-LTB5, which in turn is catabolized to
20-COOH-LTB5. The structures of the two catabolites were established by
UV-absorbance, behavior on reverse-phase high- performance liquid
chromatography, enzymatic analysis of human neutrophils, and gas
chromatography-mass spectrometry. In vitro, formation of LTB4 was delayed
and formation of its catabolites was depressed by exogenous
eicosapentaenoic acid. By supplementing the diet of six volunteers with 5 g
eicosapentaenoic acid/day for 7 days, eicosapentaenoic acid quadrupled in
neutrophil phospholipid fatty acids. Consequently, LTB5, 20-OH-LTB5, and
20-COOH-LTB5 were detected ex vivo. In contrast to the findings in vitro,
however, levels of LTB4, 20-OH-LTB4, and 20-COOH-LTB4 were unaltered by the
dietary intervention. Thus, in vitro, but not ex vivo, addition of
eicosapentaenoic acid, and subsequent formation of LTB5, impeded catabolism
of proinflammatory LTB4.