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Adenosine

An Endogenous Inhibitor of Arachidonic Acid Release and Leukotriene Biosynthesis in Human Neutrophils

  • Chapter
Lipoxygenases and their Metabolites

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 447))

Abstract

Insufficient arachidonic acid availability limits the biosynthesis of leukotriene B4 (LTB4) in polymorphonuclear leukocytes (PMN) stimulated with soluble agonists. We report that endogenous adenosine (Ado) present in human PMN suspensions suppresses LTB4 biosynthesis induced by platelet-activating factor (PAF). The blockade of the effects of Ado with an antagonist, theophylline, during the incubation of PMN resulted in significant enhancement of arachidonic acid release and LTB4 biosynthesis upon PAF stimulation. The enhancement of LTB4 biosynthesis in theophylline-treated PMN was reversed upon addition of exogenous Ado and analogues of Ado; 5’(N-ethyl)caboxamidoadenosine (IC50= 6 nM) was more potent than Ado (IC50 = 60 nM) which was more potent than N6-cyclopentyladenosine (IC50 = 330 nM) in inhibiting LTB4 biosynthesis, a pharmacological profile which is consistent with the involvement of the Ado A2 receptor type. The mechanism of inhibition of arachidonic acid release by Ado was investigated. Immunoblot analysis of cytosolic phospholipase A2 (cPLA2) in PMN fractions demonstrated that theophylline failed to further increase the translocation of the enzyme to particulate fractions (12,000 x g and 180,000 x g pellets) upon PAF stimulation. Moreover, the stimulation of intact PMN with PAF caused a decreased electrophoretic mobility of the cPLA2 and the presence of theophylline did not alter this mobility shift. Together, these results demonstrate that elevated endogenous Ado, acting through A2 receptors, suppresses arachidonic acid release and LTB4 biosynthesis induced by PAF. These data provide an explanation for the relative inability of soluble agonists to trigger leukotriene biosynthesis in human PMN suspensions and support the concept that Ado, by suppressing PMN functions, acts as a physiological anti-inflammatory agent.

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References

  1. Cronstein, B. N. (1994) J. Appl. Physiol 76, 5–13.

    PubMed  CAS  Google Scholar 

  2. van Waeg, G., and Van den Berghe, G. (1991) J. Clin. Invest. 87, 305–312.

    Article  PubMed  Google Scholar 

  3. Cronstein, B. N., Kramer, S. B., Weissmann, G., and Hirschhorn, R. (1983) J. Exp. Med. 158, 1160–1177.

    Article  PubMed  CAS  Google Scholar 

  4. Salmon, J. E., and Cronstein, B. N. (1990) J. Immunol. 145, 2235–2240.

    PubMed  CAS  Google Scholar 

  5. Cronstein, B. N., Daguma, L., Nichols, D., Hutchison, A. J., and Williams, M. (1990) J. Clin. Invest. 85, 1150–1157.

    Article  PubMed  CAS  Google Scholar 

  6. Cronstein, B. N., Levin, R. L, Belanoff, J., Weissmann, G., and Hirschhorn, R. (1986) J. Clin. Invest. 78, 760–770.

    Article  PubMed  CAS  Google Scholar 

  7. Bazzoni, G., Dejana, E., and Del Maschio, A. (1991) Blood 77, 2042–2048.

    PubMed  CAS  Google Scholar 

  8. Cronstein, B. N., Haines, K. A., Kolasinski, S., and Reibman, J. (1992) Blood 80, 1052–1057.

    PubMed  CAS  Google Scholar 

  9. Wollner, A., Wollner, S., and Smith, J. B. (1993) A m. J. Resp. Cell Mol. Biol. 9, 179–185.

    CAS  Google Scholar 

  10. Bouma, M. G., Jeunhomme, T. M. M.A., Boyle, D. L., Dentener, M. A., Voitenok, N. N., van den Wildenberg, F. A. J.M., and Buurman, W. A. (1997) J. Immunol. 158, 5400–5408.

    PubMed  CAS  Google Scholar 

  11. VanCalker, D., Muller, M., and Hamprecht, B. (1979) J. Neuwchem. 33, 999–1005.

    Article  CAS  Google Scholar 

  12. Borgeat, P., and Naccache, P. H. (1990) Clin. Biochem. 23, 459–468.

    Article  PubMed  CAS  Google Scholar 

  13. Clancy, R. M., Dahinden, C. A., and Hugli, T. E. (1983) Proc. Natl. Acad. Sci. USA 80, 7200–7204.

    Article  PubMed  CAS  Google Scholar 

  14. Dahinden, C. A., Zingg, J., Maly, F. E., and de Weck, A. L. (1988) J. Exp. Med. 161, 1281–1295.

    Article  Google Scholar 

  15. DiPersio, J. F., Billing, P., Williams, R., and Gasson, J. C. (1988) J. Immunol. 140, 4315–4322.

    PubMed  CAS  Google Scholar 

  16. McColl, S. R., Krump, E., Naccache, P. H., Poubelle, P. E., Braquet, P., Braquet, M., and Borgeat, P. (1991) J. Immunol. 146, 1204–1211.

    PubMed  CAS  Google Scholar 

  17. McDonald, P. P., Pouliot, M., Borgeat, P., and McColl, S. R. (1993) J. Immunol. 151, 6399–6409.

    PubMed  CAS  Google Scholar 

  18. Surette, M. E., Palmantier, R., Gosselin, J., and Borgeat, P. (1993) J. Exp. Med. 178, 1347–1355.

    Article  PubMed  CAS  Google Scholar 

  19. Salari, H., Braquet, P., Naccache, P. H., and Borgeat, P. (1985) Inflammation 9, 127–138.

    Article  PubMed  CAS  Google Scholar 

  20. Krump, E., and Borgeat, P. (1994) Biochim. Biophys. Acta 1213, 135–139.

    PubMed  CAS  Google Scholar 

  21. Balsinde, J., Diez, E., Schüller, A., and Mollinedo, F. (1988) J. Biol. Chem. 236, 1929–1936.

    Google Scholar 

  22. Marshall, L. A., and Roshak, A. (1993) Biochemistry and Cell Biology—Biochimie et Biologie Cellulaire 71, 331–339.

    Article  PubMed  CAS  Google Scholar 

  23. Ramesha, C. S., and Ives, D. L. (1993) Biochim. Biophys. Acta 1168, 37–44.

    PubMed  CAS  Google Scholar 

  24. Doerfler, M. E., Weiss, J., Clark, J. D., and Elsbach, P. (1994) J. Clin. Invest. 93, 1583–1591.

    Article  PubMed  CAS  Google Scholar 

  25. Durstin, M., Durstin, S., Molski, T. F. P., Becker, E. L., and Shaafi, R. I. (1994) Proc. Natl. Acad. Sci. USA 91, 3142–3146.

    Article  PubMed  CAS  Google Scholar 

  26. Krump, E., Lemay, G., and Borgeat, P. (1996) Br. J. Pharmacol. 117, 1639–1644.

    PubMed  CAS  Google Scholar 

  27. Jacobson, K. A., van Galen, P. J. M., and Williams, M. (1992) J. Med. Chem. 35, 407–422.

    Article  PubMed  CAS  Google Scholar 

  28. Gurden, M. F., Coates, J., Ellis, F., Evans, B., Foster, M., Hornby, E., Kennedy, L, Martin, D. P., Strong, P., Vardey, C. J., and Wheeldon, A. (1993) Br. J. Pharmacol. 109, 693–698.

    PubMed  CAS  Google Scholar 

  29. Akbar, M., Okajima, F., Tomura, H., Shimegi, S., and Kondo, Y. (1994) Mol. Pharmacol. 45, 1036–1042.

    PubMed  CAS  Google Scholar 

  30. Shimegi, S., Okajima, F., and Kondo, Y. (1994) Biochem. J. 299, 845–851.

    PubMed  CAS  Google Scholar 

  31. Lin, L. L., Wartmann, M., Lin, A. Y, Knopf, J. L., Seth, A., and Davis, R. J. (1993) Cell 72, 269–278.

    Article  PubMed  CAS  Google Scholar 

  32. Nemenoff, R. A., Winitz, S., Qian, N. X., Vanputten, V., Johnson, G. L., and Heasley, L. E. (1993) J. Biol. Chem. 268, 1960–1964.

    PubMed  CAS  Google Scholar 

  33. Sharp, J. D., White, D. L., Chiou, X. G., Goodson, T., Gamboa, G. C, Mcclure, D., Burgert, S., Hoskins, J., Skatrud, P. L., Sportsman, J. R., Becker, G. W, Kang, L. H., Roberts, E. F., and Kramer, R. M. (1991) J. Biol. Chem. 266, 14850–14853.

    PubMed  CAS  Google Scholar 

  34. Clark, J. D., Lin, L.-L., Kriz, R. W., Ramesha, C. S., Sultzman, L. A., Lin, A. Y, Milona, N., and Knopf, J. L. (1991) Cell 65, 1043–1051.

    Article  PubMed  CAS  Google Scholar 

  35. Wijkander, J., and Sundler, R. (1992) Biochem. Biophys. Res. Commun. 184, 118–124.

    Article  PubMed  CAS  Google Scholar 

  36. Nalefski, E. A., Sultzman, L. A., Martin, D. M., Kriz, R. W, Towler, P. S., Knopf, J. L., and Clark, J. D. (1994) J. Biol. Chem. 269, 18239–18249.

    PubMed  CAS  Google Scholar 

  37. Peters-Golden, M., and Mcnish, R. W. (1993) Biochem. Biophys. Res. Commun. 196, 147–153.

    Article  PubMed  CAS  Google Scholar 

  38. Pouliot, M., McDonald, P. P., Krump, E., Mancini, J. A., McColl, S. R., Weech, P. K., and Borgeat, P. (1996) Eur. J. Biochem. 238, 250–258.

    Article  PubMed  CAS  Google Scholar 

  39. Woods, J. W., Evans, J. F., Ethier, D., Scott, S., Vickers, P. J., Hearn, L., Heibein, J. A., Charleson, S., and Singer, L I. (1993) J. Exp. Med. 178, 1935–1946.

    Article  PubMed  CAS  Google Scholar 

  40. Brock, T. G., Paine, R., and Petersgolden, M. (1994) J. Biol Chem. 269, 22059–22066.

    PubMed  CAS  Google Scholar 

  41. Iannone, M. A., Wolberg, G., and Zimmerman, T. (1989)J. Biol. Chem. 264, 20177–20180.

    PubMed  CAS  Google Scholar 

  42. Revan, S., Montesinos, M. C, Naime, D., Landau, S., and Cronstein, B. N. (1996) J. Biol. Chem. 271, 17114–17118.

    Article  PubMed  CAS  Google Scholar 

  43. Claesson, H.-E, Lundberg, U., and Malmsten, C. (1981) Biochem. Biophys. Res. Commun. 99, 1230–1237.

    Article  PubMed  CAS  Google Scholar 

  44. Ham, E. A., Soderman, D. D., Zanetti, M. E., Dougherty, H. W., McCauley, E., and Kuehl, F. A., Jr. (1983) Proc. Natl. Acad. Sci. USA 50, 4349–4353.

    Article  Google Scholar 

  45. Daniels, R. H., Bird, I. N., Hill, M. E., and Finnen, M. J. (1993) Biochem. Pharmacol. 45, 1613–1620.

    Article  PubMed  CAS  Google Scholar 

  46. Nielson, C. P., Bayer, C, Hodson, S., and Hadjokas, N. (1992) J. Immunol. 149, 4036–4040.

    PubMed  CAS  Google Scholar 

  47. Fonteh, A. N., Winkler, J. D., Torphy, T. J., Heravi, J., Undem, B. J., and Chilton, F. H. (1993) J. Immunol. 151, 339–350.

    PubMed  CAS  Google Scholar 

  48. Laghi-Pasini, F., Capecci, P. L., Pasqui, A. L., Ceccatelli, L., Mazza, S., Gistri, A., and Di Perri, T. (1990) Exp. Gerontol. 25, 383–391.

    Article  PubMed  CAS  Google Scholar 

  49. Capuozzo, E., Crifo, C., Siems, W., and Salerno, C. (1993) Biochem. Mol. Biol. Int. 30, 1071–1079.

    PubMed  CAS  Google Scholar 

  50. Tsuruta, S., Ito, S., and Mikawa, H. (1992) Cell. Signal. 4, 543–551.

    Article  PubMed  CAS  Google Scholar 

  51. Schatz-Munding, M., Hatzelmann, A., and Ullrich, V. (1991) Eur. J. Biochem. 197, 487–493.

    Article  PubMed  CAS  Google Scholar 

  52. Hatzelmann, A., Haurand, M., and Ullrich, V. (1990) Biochem. Pharmacol. 39, 559–567.

    Article  PubMed  CAS  Google Scholar 

  53. Krump, E., Pouliot, M., Naccache, P. H., and Borgeat, P. (1995) Biochem. J. 310, 681–688.

    PubMed  CAS  Google Scholar 

  54. Burch, R. M., Luini, A., and Axelrod, J. (1986) Proc. Natl. Acad. Sci. USA 83, 7201–7205.

    Article  PubMed  CAS  Google Scholar 

  55. Ho, A. K., and Klein, D. C. (1987) J. Biol. Chem. 262, 11764–11770.

    PubMed  CAS  Google Scholar 

  56. Slivka, S. R., and Insel, P. A. (1988) J. Biol. Chem. 263, 14640–14647.

    PubMed  CAS  Google Scholar 

  57. Brooks, R. C, McCarthy, K. D., Lapetina, E. G., and Morell, P. (1989) J. Biol. Chem. 264, 20147–20153.

    PubMed  CAS  Google Scholar 

  58. Balsinde, J., Fernandez, B., and Diez, E. (1990) J. Immunol. 144, 4298–4304.

    PubMed  CAS  Google Scholar 

  59. Ford-Hutchinson, A. W. (1990) Crit. Rev. Immunol. 10, 1–12.

    PubMed  CAS  Google Scholar 

  60. Cronstein, B. N., Eberle, M. A., Gruber, H. E., and Levin, R. I. (1991) Proc. Natl. Acad. Sci. USA 88, 2441–2445.

    Article  PubMed  CAS  Google Scholar 

  61. Cronstein, B. N., Naime, D., and Ostad, E. (1993) J. Clin. Invest. 92, 2675–2682.

    Article  PubMed  CAS  Google Scholar 

  62. Gadangi, P., Longaker, M., Naime, D., Levin, R. L, Recht, P. A., Montesinos, M. C, Buckley, M. T., Carlin, G., and Cronstein, B. N. (1996) J. Immunol. 156, 1937–1941.

    PubMed  CAS  Google Scholar 

  63. Chilton, F. H., Ellis, J. H., Olson, S. C, and Wykle, R. L. (1984) J. Biol. Chem. 259, 12014–12019.

    PubMed  CAS  Google Scholar 

  64. Suga, K., Kawasaka, T., Blank, M. L., and Snyder, F. (1990) J. Biol. Chem. 265, 12363–12371.

    PubMed  CAS  Google Scholar 

  65. Borgeat, P., Picard, S., Vallerand, P., Bourgoin, S., Odeimat, A., Sirois, P., and Poubelle, P. E. (1990) In: Methods in Enzymology.(R. C. Murphy and F. A. Fitzpatrick, Eds.) Academic Press, New York, vol. 187, pp. 98–116.

    Google Scholar 

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Authors and Affiliations

  1. Centre de Recherche en Rhumatologie et Immunologie, Centre de Recherche du Pavillon CHUL and Université Laval, 2705 Boul, Laurier, Québec, Canada, GlV 4G2

    Eric Krump & Pierre Borgeat

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  1. Eric Krump
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  2. Pierre Borgeat
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  1. Free University of Berlin, Berlin, Germany

    Santosh Nigam

  2. Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada

    Cecil R. Pace-Asciak

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© 1999 Kluwer Academic/Plenum Publishers, New York

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Krump, E., Borgeat, P. (1999). Adenosine. In: Nigam, S., Pace-Asciak, C.R. (eds) Lipoxygenases and their Metabolites. Advances in Experimental Medicine and Biology, vol 447. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4861-4_10

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  • DOI: https://doi.org/10.1007/978-1-4615-4861-4_10

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-0-306-46044-9

  • Online ISBN: 978-1-4615-4861-4

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