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Bee venom melittin blocks neutrophil O2 − production

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Abstract

Bee vemon (BV) is used in folk medicine to treat arthritis. It has antiinflammatory effects in animal models of rheumatic disease. We have studied the effects of BV on human neutrophil production of superoxide (O2 −) and hydrogen peroxide, finding potent, nontoxic, dose-dependent production inhibition. Melittin, the major fraction of BV (50–70%) shows high-affinity calmodulin binding Kd 3 nM). Drugs which bind calmodulin, such as trifluoperazine, inhibit O2 − production by human neutrophils. For these reasons we have investigated the effect of melittin and other BV peptides on O2 − production by human peripheral blood leukocytes. We show that melittin inhibited O2 − production both pre- and poststimulation in contrast to other BV fractions which were without effect. Oxygen radicals and their derivatives from inflammatory cells are implicated in the tissue damage occurring during inflammation. The inhibition is due to a direct effect on cells, and not indicator medium, dismutation, toxic or scavenging effects. We propose that melittin may serve as a prototype small (mol wt 1280), cationic, amphipathic, calmodulin-binding, membrane-active, superoxide-production-inhibiting peptide, providing a model for peptides which could have a role in in vivo regulation of radical production.

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References

  1. Beck, B. 1935. Bee Venom Therapy. Appleton-Century Company, New York.

    Google Scholar 

  2. Yoirish, N. 1977. The Curative Properties of Honey and Bee Venom. New Glide Publications, San Francisco.

    Google Scholar 

  3. Chang, Y. H., andM. L. Bliven. 1979. Antiarthritic effect of bee venom.Agents Actions 9:205–211.

    Google Scholar 

  4. Lorenzetti, O. J., B. Fortenberry, andE. Busby. 1972. Influence of bee venom in the adjuvant induced arthritic rat model.Res. Commun. Chem. Pathol. Pharmacol 4:399–352.

    Google Scholar 

  5. Lockshin, M. D. 1981. Special article. The unproven remedies committee.Arthritis Rheum. 24:1188–1190.

    Google Scholar 

  6. McCord, J. M., K. Wong, S. H. Stokes, W. F. Petrone, andD. English. 1980. Superoxide and inflammation: A mechanism for the antiinflammatory activity of superoxide dismutase.Acta Physiol. Scand. Suppl. 494:25–30.

    Google Scholar 

  7. McCord, J. M. andK. Wong. 1979. Phagocyte production free radicals: Roles in cytotoxicity and inflammation.Ciba Found. Symp. 65:343–369.

    Google Scholar 

  8. Somerfield, S. D., J. L. Stach, C. Mraz, F. Gervais, andE. Skamene. 1984. Bee venom inhibits superoxide production by human neutrophils.Inflammation 8, (4):385–391.

    Google Scholar 

  9. Singal, P. K., N. Kapur, andK. S. Dhillon. 1982. Role of free radicals in catecholamine-induced cardiomyopathy.Can. J. Physiol. Pharmacol. 60:1390–1387.

    Google Scholar 

  10. Donaldson, J., D. McGregor, andF. La Bella. 1982. Manganese Neurotoxicity: A model for free radical-mediated neurodegeneration.Can. J. Physiol. Pharmacol. 9:443–445.

    Google Scholar 

  11. Butterfield, J. D., andC. P. McGraw. 1978. Free radical pathology.Stroke 9:443–445.

    Google Scholar 

  12. Demopoulos, H. B., E. S. Flamm, andD. D. Pietronigro. 1980. The free radical pathology and the microcirculation in the major central nervous system disorders.Acta Physiol. Scand. Suppl. 492:91–119.

    Google Scholar 

  13. Lunec, J., S. P. Halloran, R. G. White, andT. L. Dormandy. 1981. Free radical oxidation (peroxidation) products in serum and synovial fluid in rheumatoid arthritis.J. Rheumatol. 8:233–245.

    Google Scholar 

  14. McCord, J. M. 1974. Free radicals and inflammation: Protection of synovial fluid by superoxide dismutase.Science 185:529–531.

    Google Scholar 

  15. Hyrst, N. P., B. Bessac, andG. Nuki. 1984. Monocyte superoxide anion production in rheumatoid arthritis: Preliminary evidence for enhanced rates of superoxide anion production by monocytes from patients receiving penicillamine, sodium aurothiomalate, and corticosteroids.Ann. Rheum. Dis. 43:28–33.

    Google Scholar 

  16. Ferrante, A., andY. H. Thong. 1980. Optimal conditions for simultaneous purification of mononuclear and polymorphonuclear leukocytes from human peripheral blood by HypaqueFicoll method.J. Immunol. Methods 36:109–117.

    Google Scholar 

  17. Benton, A. W., R. A. Morse, andJ. D. Stewart. 1963. Venom collection from honey bees.Science 142:228–230.

    Google Scholar 

  18. Bobik, A., J. Campbell, P. Snow, andP. J. Little. 1983. The effects of endogenous phospholipase A2 activation on beta adrenoceptor function in cardiac cells.J. Mol. Cell. Cardiol. 15:759–768.

    Google Scholar 

  19. Cohen, H. J., andM. E. Chovaniec. 1978. Superoxide generation by digitonin stimulated guinea pig granulocytes. A basis for a continuous assay monitoring superoxide production and for the study of the activation of the generating system.J. Clin. Invest. 61:1081–1087.

    Google Scholar 

  20. Fridovich, I. 1970. Quantitative aspects of the production of superoxide anion radical by milk xanthine oxidase.J. Biol. Chem. 215:4053–4057.

    Google Scholar 

  21. Takeshige, K., andS. Minakami. 1981. Involvement of calmodulin in phagocytic respiratory burst of leukocytes.Biochem. Biophys. Res. Commun. 99:484–490.

    Google Scholar 

  22. Smith, R. J., B. J. Bowman, andS. S. Iden. 1981. Effects of trifluoperazine on human neutrophil function.Immunology 44:677–684.

    Google Scholar 

  23. Smolen, J. E. andG. Weissmann. 1981. The roles of extracellular and intracellular calcium in lysosomal enzyme release and superoxide anion generation by human polymorphonuclear leukocytes.Biochim. Biophys. Acta 677:512–520.

    Google Scholar 

  24. Menander-Huber, K. B. 1980. Double-blind controlled clinical trials in man with bovine copper-zinc superoxide dismutase (Orgotein).In Biological and Clinical Aspects of superoxide and superoxide Dismutase. W. H. Bannister, J. V. Bannister, editors. Elsevier/North Holland, Amsterdam. 408–423.

    Google Scholar 

  25. Comte, M., Y. Maulet, andJ. A. Cox, 1983. Ca2+-dependent high-affinity complex formation between calmodulin and melittin.Biochem. J. 209:269–272.

    Google Scholar 

  26. Barbior, B. M. 1984. The respiratory burst of phagocytes.J. Clin. Invest. 73:599–601.

    Google Scholar 

  27. Katoh, N., R. L. Raynor, B. C. Wise, R. C. Schatzman, R. S. Turner, D. M. Helfman, J. N. Fain, andJ. Kuo 1982. Inhibition by melittin of phospholipid-sensitive and calmodulinsensitive Ca2+ -dependent protein kinases.Biochem. J. 202:217–224.

    Google Scholar 

  28. Mori, T., Y. Takai, R. Minakuchi, B. Yu, andY. Nishizuka. 1980. Inhibitory action of chlorpromazine, dibucaine and other phospholipid-interacting drugs on calcium-activated, phospholipid-dependent protein kinases.J. Biol Chem. 255:8378–8380.

    Google Scholar 

  29. Jones, H. P., G. Chai, W. F. Petrone, andJ. M. McCord. 1982. Calmodulin-dependent stimulation of the NADPH oxidase of human neutrophils.Biochim. Biophys. Acta 714:152–156.

    Google Scholar 

  30. MacNeil, S., S. W. Walker, B. L. Brown, andS. Tomlinson. 1982. Evidence that calmodulin may be involved in phytohaemagglutinin-stimulated lymphocyte division.Biosci. Rep. 2:891–897.

    Google Scholar 

  31. Castagna, M., Y. Takai, K. Kaibucht, K. Sano, U. Kikkawa, andY. Nishizuka. 1982. Direct activation of calcium activated phospholipid-dependent protein kinase by tumour producing phorbol esters.J. Biol. Chem. 257:7847–7851.

    Google Scholar 

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Author notes

  1. Stanley D. Somerfield

    Present address: Department of Immunobiology, University of Auckland, Private Bag, Auckland, New Zealand

Authors and Affiliations

  1. Montreal General Hospital Research Institute, 1650 Cedar Avenue, H3G 1A4, Montreal, Quebec, Canada

    Stanley D. Somerfield, Jean -Louis Stach, Francine Gervais & Emil Skamene

  2. Middlebury, Vermont

    Charles Mraz

Authors
  1. Stanley D. Somerfield
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  2. Jean -Louis Stach
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  3. Charles Mraz
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  4. Francine Gervais
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  5. Emil Skamene
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Additional information

Supported by grants from the Medical Research Council of Canada (No. 6431), Arthritis Society of Canada (No. 5-261-83), Arthritis Foundation of New Zealand and Rose Hellaby Trust.

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Somerfield, S.D., Stach, J.L., Mraz, C. et al. Bee venom melittin blocks neutrophil O2 − production. Inflammation 10, 175–182 (1986). https://doi.org/10.1007/BF00915999

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