Differences between the Effects of f-Met-Leu-Phe and Leukotriene B4 on Phosphoinositide Turnover and Their Relationship to Calcium Mobilization and Protein Kinase C Activation

  • Ramadan I. Sha’afi
  • Mario Volpi
  • Paul H. Naccache
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)


It is generally accepted that the mobilization and metabolism of arachidonic acid are involved in the activation and/or modulation of the neutrophil’s responses and that the major biological activities of arachidonic acid are mediated by the ability of leukotriene B4 to alter calcium homeostasis (for a review and original citations, see Bach, 1983). This conclusion is based on various experimental results. First, the biological activities of exogenously added arachidonic acid and some of its metabolites have been demonstrated. Second, the activation of the neutrophils by chemotactic factors can be modulated by certain lipase and lipoxygenase inhibitors. Third, chemotactic factors cause the release of arachidonic acid previously incorporated in phospholipids and stimulate its subsequent metabolism including the generation of leukotriene B4. Fourth, the exogenous addition of leukotriene B4 to neutrophils increases the intracellular concentration of free calcium, with characteristics similar to those of its biological activities. This increase occurs through the release of calcium from internal stores, by displacement of previously bound calcium from membranous and other sites, and from the extracellular medium through an increase in the plasma membrane permeability to calcium.


Arachidonic Acid Phosphatidic Acid Free Calcium Chemotactic Factor Calcium Mobilization 
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  1. Bach, M. K., 1983, The Leukotrienes and Their Structure, Actions and Role in Disease, Upjohn, Kalamazoo, MI.Google Scholar
  2. Bormann, B.J., Huang, C.-K., Mackin, W.M., and Becker, E.L., 1984, Receptor-mediated activation of phospholipase A2 in rabbit neutrophil plasma membrane, Proc. Natl. Acad. Sci. U.S.A. 81:767–770.PubMedCrossRefGoogle Scholar
  3. Claesson, H.-F., 1982, Leukotrienes A4 and B4 stimulate the formation of cyclic AMP in human leukocytes, FEBS Lett. 139:305–308.PubMedCrossRefGoogle Scholar
  4. Feinstein, M. B., and Sha’afi, R. I., 1983, Role of calcium in arachidonic acid metabolism and in the actions of arachidonic acid-derived metabolites, in Calcium and Cell Function, Vol. IV (W. Y. Cheung, ed.), Academic Press, New York, pp. 337–376.Google Scholar
  5. Gilman, A.G., 1984, G proteins and dual control of adenylate cyclase, Cell 36:577–579.PubMedCrossRefGoogle Scholar
  6. Holmes, R.P., and Yoss, N.L., 1983, Failure of phosphatidic acid to translocate Ca2+ across phos-phatidylcholine membranes, Nature 305:637–638.PubMedCrossRefGoogle Scholar
  7. Kishimoto, A., Kajikawa, N., Shiota, M., and Nishizuka, Y., 1983, Proteolytic activation of calcium-activated, phospholipid-dependent protein kinase by calcium-dependent neutral protease, J. Biol. Chem. 258:1156–1164.PubMedGoogle Scholar
  8. Lad, R.M., Glovsky, M.M., Smiley, P.A., Klempner, M., Reisinger, D.M., and Richard, J.H., 1984, The ß-adrenergic receptor in the human neutrophil plasma membrane: Receptor-cyclase uncoupling is associated with amplified GTP activation, J. Immunol. 132:1466–1471.PubMedGoogle Scholar
  9. Michell, R.H., and Kirk, C.J., 1982, The unknown meaning of receptor-stimulated inositol lipid metabolism, Trends. Pharmacol. Sci. 3:1490–1499.Google Scholar
  10. Palmblad, J., Maimsten, C.L., Uden, A., Radmark, O., Engsted, E.L., and Samuelsson, B., 1981, Leukotriene B4 is a potent and stereospecific stimulator of neutrophil chemotaxis and adherence. Blood 58:658–661.PubMedGoogle Scholar
  11. Serhan, C.N., Fridovich, J., Goetzl, E.J., Dunham, P.B., and Weiss: n, G., 1982, Leukotriene B4 and phosphatidic acid are calcium ionophores: Studies employing arsenazo III in liposomes, J. Biol. Chem. 257:4746–4752.PubMedGoogle Scholar
  12. Sha’afi, R. I., and Naccache, P. H., 1985, Relationships between calcium, arachidonic acid metabolites and neutrophil activation, in: Calcium in Biological Systems (R. P. Rubin, G. Weiss, and J. W. Putney, Jr., eds.), Plenum Press, New York, pp. 137–145.CrossRefGoogle Scholar
  13. Sha’afi, R.L., White, J.R., Molski, T.F.P., Shefcyk, J., Volpi, M., Naccache, P.H., and Feinstein, M.B., 1983, Phorbol 12-myristate 13-acetate activates rabbit neutrophils without an apparent rise in the level of intracellular free calcium, Biochem. Biophys. Res. Commun. 114:638–645.CrossRefGoogle Scholar
  14. Streb, H., Irvine, R.F., Berridge, M.J., and Shulz, I., 1983, Release of Ca2+ from a non-mitochondrial intracellular store in pancreatic acinar cells by inositol-l,4,5-triphosphate, Nature 306:67–69.PubMedCrossRefGoogle Scholar
  15. Volpi, M., Yassin, R., Naccache, P.H., and Sha’afi, R.I., 1983, Chemotactic factor causes rapid decrease in phosphatidyl inositol 4.5-bis phosphate and phosphatidyl inositol 4-monophosphate in rabbit neutrophils, Biochem. Biophys. Res. Commun. 112:957–964.PubMedCrossRefGoogle Scholar
  16. White, J.R., Naccache, P.H., Molski, T.F.P., Borgeat, P., and Sha’afi, R.I., 1983, Direct demonstration of increased intracellular concentration of free calcium in rabbit and human neutrophils following stimulation by chemotatic factors, Biochem. Biophys. Res. Commun. 113:44–50.PubMedCrossRefGoogle Scholar
  17. White, J.R., Huang, C.-K., Hill, J.M., Naccache, P.H., Becker, E.L., and Sha’afi, R.I., 1984, Effect of phorbol 12-myristate 13-acetate and its analogue 4α-phorbol 12,13-didecanoate on protein phosphorylation and lysosomal enzyme release in rabbit neutrophils, J. Biol. Chem. 259:8605–8611.PubMedGoogle Scholar
  18. Yassin, R., Shefcyk, J., Tao, W., White, J.R., Molski, T.F.P., Naccache, P.H., and Sha’afi, R.I., 1984, Actin association with the cytoskeleton in human and rabbit neutrophils: Possible signal for mediating actin polymerization, Fed. Proc. 43:1507.Google Scholar

Copyright information

© Springer Science+Business Media New York 1985

Authors and Affiliations

  • Ramadan I. Sha’afi
    • 1
  • Mario Volpi
    • 1
  • Paul H. Naccache
    • 2
  1. 1.Department of PhysiologyUniversity of Connecticut Health CenterFarmingtonUSA
  2. 2.Department of PathologyUniversity of Connecticut Health CenterFarmingtonUSA

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