Leukotriene B: a biologically active release product of polymorphonuclear leukocytes

  • A. W. Ford-Hutchinson
  • M. A. Bray
  • M. E. Shipley
  • M. V. Doig
  • M. J. H. Smith
Part of the Inflammation: Mechanisms and Treatment book series (FTIN, volume 4)


Arachidonic acid (AA) may be metabolized either by cyclo-oxygenase enzyme systems to form prostaglandins and thromboxanes or by lipoxygenase enzymes to produce mono-, di- and trihydroxy fatty acids via either hydroperoxy or epoxide intermediates1. The biological functions of the products of lipoxygenase pathways of AA metabolism are largely unknown. Activities which have been ascribed to these compounds include SRS-A activity2; chemotactic and chemokinetic activities towards polymorphonuclear leukocytes (PMNs) and eosinophils3; a possible involvement in T lymphocyte activation4 and regulation of the biosynthesis5 of PGI2. PMNs have been shown to release a number of products of the lipoxygenase pathways of AA metabolism when exposed to stimuli6,7 such as the calcium ionophore A23187. The present work describes the release of chemokinetic and aggregating activity from rat and human PMNs exposed to calcium ionophore A23187 and demonstrates that these activities are due to leukotriene B, a metabolite of AA produced by lipoxygenase enzymes.


Arachidonic Acid Trimethylsilyl Ether Calcium Ionophore A23187 Lipoxygenase Pathway Nordihydroguaiaretic Acid 
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  1. 1.
    Jones, R. L.(1979).Pathwaysofarachidonicacidmetabolism. InRainsford, K. D.and Ford-Hutchinson, A. W. (eds.) Prostaglandins and Inflammation, pp 19–26. (Basel: Birkhauser-Verlag)CrossRefGoogle Scholar
  2. 2.
    Murphy, R. C. Hammarstrom, S. and Samuelsson, B. (1979). Leukotriene C: a slow-reacting substance from murine mastocytoma cells. Proc. Natl. Acad. Sci. (USA), 76, 4275CrossRefGoogle Scholar
  3. 3.
    Goetzl, E. J. and Sun, F.F. (1979). Generation of unique monohydroxy-eicosatetraenoic acids from arachidonic acid by human neutrophils. J. Exp. Med., 150, 406PubMedCrossRefGoogle Scholar
  4. 4.
    Kelly, J. P., Johnson, M. C. and Parker, C. W. (1979). Effect of inhibitors of arachidonic acid metabolism on mitogenesis in human lymphocytes: a possible role of thromboxanes and products of the lipoxygenase pathway. J. Immunol., 122, 156–3Google Scholar
  5. 5.
    Salmon, J.A., Smith, B. R., Flower, R. J., Moncada, S. and Vane, J. R. (1978). Further studies on the enzymatic conversion of prostaglandin endoperoxides into PG12. Biochem. Biophys. Acta, 523, 252Google Scholar
  6. 6.
    Borgeat, P. and Samuelsson, B. (1979) Arachidonic acid metabolism in polymorphonuclear leukocytes: effects of ionophore A23187. Proc. Natl. Acad. Sci (USA), 76, 2148CrossRefGoogle Scholar
  7. 7.
    Stenson, W. F. and Parker, C. W. (1979) Metabolism of arachidonic acid in ionophore-stimulated neutrophils. J. Clin. Invest., 64, 1457PubMedCrossRefGoogle Scholar
  8. 8.
    Cunningham, F.M., Smith, M.J. H., Ford-Hutchinson, A. W. and Walker, J. R. (1979). Migration of peritoneal leucocytes in the rat. J. Pathol., 128, 15PubMedCrossRefGoogle Scholar
  9. 9.
    Cunningham, F. M., Ford-Hutchinson, A. W., Oliver, A.M., Smith, M. J. H. and Walker, J. R. (1978). The effects of D-penicillamine and levamisole on leucocyte Chemotaxis in the rat. Br. J. Pharmacol., 63, 119PubMedGoogle Scholar
  10. 10.
    Bray, M. A., Ford-Hutchinson, A. W., Shipley, M. E. and Smith, M. J. H. (1980). Calcium ionophore A23187 induces release of chemokinetic and aggregating factors from polymorphonuclear leucocytes. Br. J. Pharmacol. (In press)Google Scholar
  11. 11.
    Cunningham, F. M., Shipley, M. E. and Smith, M. J. H. (1980). Aggregation of rat polymorphonuclear leucocytes in vitro. J. Pharm. Pharmacol., 32, 377Google Scholar
  12. 12.
    Ford-Hutchinson, A. W., Bray, M. A. and Smith, M. J. H. (1979). The aggregation of rat neutrophils by arachidonic acid: a possible bioassay for lipoxygenase activity. J. Pharm. Pharmacol., 12, 868CrossRefGoogle Scholar
  13. 13.
    Smith, M.J. H. and Walker, J. R. (1980). The effects of some anti-rheumatic drugs on an in vitro model of human polymorphonuclear leukocyte chemokinesis. Br. J. Pharmacol., 69, 473PubMedGoogle Scholar
  14. 14.
    O’Faherty, J. T.,Showell, H. J., Becker, E. L. and Ward, P. A. (1979). Neutrophil aggregation and degranulation: effect of arachidonic acid. Am.J.Pathol., 95, 433Google Scholar
  15. 15.
    O’Flaherty, J. T., Showell, H. J., Becker, E. L. and Ward, P. A. (1979). Role of arachidonic acid derivatives in neutrophil aggregation: a hypothesis. Prostaglandins, 17, 915PubMedCrossRefGoogle Scholar
  16. 16.
    Siegel, M. I., McConnell, R. T. and Cuatrecasas, P. (1979). Aspirin-like drugs interfere with arachidonate metabolism by inhibition of the 12-hydroperoxy-5, 8, 10, 14-eicosatetraenoic acid peroxidase activity of the lipoxygenase pathway. Proc. Natl. Acad. Sci. (USA), 76, 774CrossRefGoogle Scholar
  17. 17.
    Tobias, L. D. and Hamilton, J. G. (1979). The effect of 5,8,11,14-eicosatetraynoic acid on lipid metabolism. Lipids, 14, 181PubMedCrossRefGoogle Scholar
  18. 18.
    Tapell, A. L., Lundberg, W. and Boyer, P. D. (1953) Effects of temperature and antioxidants upon the lipoxidase-catalysed oxidation of sodium linoleate. Arch. Biochem. Biophys., 42, 293CrossRefGoogle Scholar
  19. 19.
    Hamberg, M. and Samuelsson, B. (1974). Prostaglandin endoperoxides: novel transformation of arachidonic acid in human platelets. Proc. Natl. Acad. Sci. (USA), 71, 3400CrossRefGoogle Scholar
  20. 20.
    Higgs, G. A. Flower, R.J. and Vane, J. R. (1979). A new approach to anti-inflammatory drugs. Biochem. Pharmacol., 28, 1959PubMedCrossRefGoogle Scholar
  21. 21.
    Walker, J. R. and Dawson, W. (1979). Inhibition of rabbit PMN lipoxygenase activity by benoxaprofen. J. Pharm. Pharmacol., 11, 778CrossRefGoogle Scholar
  22. 22.
    Borgeat, P. and Samuelsson, B. (1979). Metabolism of arachidonic acid in polymorphonuclear leucocytes. Structural analysis of novel hydroxylated compounds. J. Biol. Chem., 254, 7865PubMedGoogle Scholar
  23. 23.
    Bokoch, G. M. and Reed, P. W. (1979). Inhibition of the neutrophil oxidative response to a chemotactic peptide by inhibitors of arachidonic acid oxygenation. Biochem. Biophys. Res. Commun., 90, 481PubMedCrossRefGoogle Scholar
  24. 24.
    Smolen, J. and Weissman, G. (1980). Lysosomal enzyme release from human granulocytes is inhibited by indomethacin and ETYA. Advances in Prostaglandins and Thromboxanes Research. (In press)Google Scholar
  25. 25.
    Valone, F. H. and Goetzl, E. J. (1978). Immunological release in the rat peritoneal cavity of lipid chemotactic and chemokinetic factors for polymorphonuclear leucocytes. J. Immunol., 120, 102PubMedGoogle Scholar

Copyright information

© MTP Press Limited 1980

Authors and Affiliations

  • A. W. Ford-Hutchinson
    • 1
  • M. A. Bray
    • 1
  • M. E. Shipley
    • 1
  • M. V. Doig
    • 1
  • M. J. H. Smith
    • 1
  1. 1.UK

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