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Inflammation

, Volume 26, Issue 5, pp 215–222 | Cite as

Dexamethasone Inhibits Apoptosis of Human Neutrophils Induced by Reactive Oxygen Species

  • Lina M. Ruiz
  • Gabriel Bedoya
  • James Salazar
  • Diana García de O
  • Pablo J. Patiño
Article

Abstract

Neutrophils are completely differentiated cells that die in tissues a few days after they migrate from the vascular compartment as a consequence of a rigouous apoptotic program. Many of the mediators produced during an inflammatory response delay neutrophil apoptosis allowing a more efficient removal of microorganisms but also favoring the tissue damage by reactive oxygen species (ROS) and lysosomal proteins released by neutrophils. Glucocorticoids delay the apoptosis of neutrophils but the mechanisms are not completely understood. To investigate the inhibition of glucocorticoids on neutrophil apoptosis we have used the glucose/glucose oxidase (G/GO) system as a constant source of hydrogen peroxide. When neutrophils are incubated in the presence of the G/GO system, a significant acceleration of their apoptotic response is observed. Preincubation with 10−6 M, 10−7 M, 10−8 M or 10−9 M of dexamethasone, negatively modulated the spontaneous and G/GO induced apoptosis of neutrophils. Then the G/GO system is a useful model to simulate the oxidative stress of neutrophils, and that the effect of DXM on neutrophil apoptosis depends, at least in part, on blocking the proapoptotic effect of ROS.

Neutrophils apoptosis reactive oxygen species dexamethasone 

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REFERENCES

  1. 1.
    Babior, B. M. and D. W. Golde. 2001. Production, distribution, and fate of neutrophils. In: Williams: Hemotology, 6th ed. Beutler, E., M. A. Lichtman, B. S. Coller, T. J. Kipps, and U. Seligsohn, eds: McGraw-Hill, New York.Google Scholar
  2. 2.
    Dahlgren, C. and A. Karlsson. 1999. Respiratory burst in human neutrophils. J. Immunol. Methods. 232(1/2):3–14.Google Scholar
  3. 3.
    Klebanoff, S. J. 1999. Oxygen metabolites from phagocytes. In: Inflammation. Basic principles and clinical correlates, 3rd ed. Gallin J. I. and R. Snyderman, eds: Raven Press, New York.Google Scholar
  4. 4.
    Babior, B. M. 1999. NADPH oxidase: an update. Blood. 93(5):1464–1476.Google Scholar
  5. 5.
    Hampton, M., B. Fadeel, and S. Orrenius. 1998. Redox regulation of the caspases during apoptosis. Ann. N.Y. Acad. Sci. 854:328–335.Google Scholar
  6. 6.
    Love, S. 1990. Oxidative stress in brain ischemia. Brain Pathol. 9(1):119–131.Google Scholar
  7. 7.
    Ward, C., T. Wong, J. Murray, I. Rahman, C. Haslett, E. Chilvers, and A. Rossi. 2000. Induction of human neutrophil apoptosis by nitric oxide donors: evidence for a caspase-dependent, cyclic-GMP-independent mechanism. Biochem. Pharmacol. 59(3):305–314.Google Scholar
  8. 8.
    Narayanan, P., K. Ragheb, G. Lawler, and J. Robinson. 1997.Defects in intracellular oxidative metabolism of neutrophils undergoing apoptosis. J. Leukoc. Biol. 61(4):481–488.Google Scholar
  9. 9.
    Oishi, K. and K. Machida. 1997. Inhibition of neutrophil apoptosis by antioxidants in culture medium. Scand. J. Immunol. 45(1):21–27.Google Scholar
  10. 10.
    Clément, M. V. and I. Stamenkovic. 1996. Superoxide anion is a natural inhibitor of Fas-mediated cell death. EMBO J. 15(2):216–225.Google Scholar
  11. 11.
    Packham, G., R. Ashmun, and J. Cleveland. 1996. Cytokines suppressed apoptosis independent of increases in reactive oxygen levels.J. Immunol. 156(8):2792–2800.Google Scholar
  12. 12.
    Leuenroth, S., C. Lee, P. Grutkoski, H. Keeping, and H. Simms. 1998. Interleukin-8-induced suppression of polymorphonuclear leukocyte apoptosis is mediated by suppressing CD95 (Fas/Apo-1) Fas-1 interactions. Surgery. 124(2):409–417.Google Scholar
  13. 13.
    Cox, G. 1995. Glucocorticoid treatment inhibits apoptosis in human neutrophils. J. Immunol. 154(9):4719–4725.Google Scholar
  14. 14.
    Liles, W. C., D. Dale, and S. Klebanoff. 1995. Glucocorticoids inhibit apoptosis of human neutrophils. Blood. 86(8):3181–3188.Google Scholar
  15. 15.
    Haslett, C. 1992. Resolution of acute inflammation and the role of apoptosis in the tissue fate of granulocytes. Clin. Sci. (London). 83(6):639–648.Google Scholar
  16. 16.
    Watson, R., O. Rotstein, A. Nathens, J. Parodo, and J. Marshall. 1997. Neutrophil apoptosis is modulated by endothelial transmigration and adhesion molecule engagement. J. Immunol. 158(2):945–953.Google Scholar
  17. 17.
    Erwig., D. Kluth, G. Walsh, and A. Rees. 1998. Initial cytokine exposure determines function of macrophages and renders them unresponsive to other cytokines. J. Immunol. 161(4):1983–1988.Google Scholar
  18. 18.
    Watson, R., H. Redmond, J. Wang, C. Condron, and D. Bouchier-Hayes. 1996. Neutrophils undergo apoptosis following ingestion of Escherichia coli. J. Immunol. 156(10):3986–3992.Google Scholar
  19. 19.
    Oseas, R. S., J. Allen, and H. H. Yang. 1982. Mechanism of dexamethasone inhibition of chemotactic factor induced granulocyte aggregation. Blood. 59(2):265–272.Google Scholar
  20. 20.
    Salazar, J. J. and B. Van Houten. 1997. Preferential mitochondrial DNA injury caused by glucose oxidase as a steady generator of hydrogen peroxide in humna fibroblast. Mutation Res. 385:139–149.Google Scholar
  21. 21.
    Nowak, D. 1990. Hydrogen peroxide release from human polymorphonuclear leukocytes measured with horseradish peroxidase and o-dianiside. Effects of various stimulators and cytochalasin B.Biomed. Biochim. Acta. 49(5):353–362.Google Scholar
  22. 22.
    Martin, D. and M. Lenardo. 1995. Morphological biochemical, flow cytometric assays of apoptosis. In: Current Protocals in Immunology. Coligan, J., A. Kruisbeeck, D. Margulies, E. Shevach, and W. Strober, eds: John Wiley & Sons, New York.Google Scholar
  23. 23.
    Homburg, C. H. E. and D. Roos. 1996. Apoptosis of neutrophils.Curr. Opin. Hematol. 3(1):94–100.Google Scholar
  24. 24.
    Moulding, D., J. Quayle, A. Hart, and S. Edwards. 1998. Mcl-1 expression in human neutrophils: regulation by cytokines and correlation with cell survival. Blood. 92(7):2495–2502.Google Scholar
  25. 25.
    Rollet-Labelle, E. M. Grange, C. Elbim, C. Marquetty, M. Gougerot-Pocidalo, and C. Pasquier. 1998. Hydroxyl radical as a potential intracellular mediator of polymorphonuclear neutrophil apoptosis. Free Radic. Biol. Med. 24(4):563–572.Google Scholar
  26. 26.
    Lundqvist-Gustafsson, H. and T. Bengtsson. 1999. Activation of the granule pool of the NADPH oxidase accelerates apoptosis in human neutrophils. J. Leukoc. Biol. 65(2):196–204.Google Scholar
  27. 27.
    Hannah, S., K. Mechlenburgh, I. Rahman, G. Bellingan, A. Greening, C. Haslett, and E. R. Chilvers. 1995. Hypoxia prolongs neutrophil survival in vitro. FEBS Lett. 372(2/3):233–237.Google Scholar
  28. 28.
    Kasahara, Y., K. Iwai, A. Yachie, K. Ohta, A. Konno, H. Seki, T. Hiyawaki, and N. Taniguchi. 1997. Involvement of reactive oxygen intermediates in spontaneous and CD95 (Fas/APO-1) mediated apoptosis of neutrophils. Blood. 89(5):1748–1753.Google Scholar
  29. 29.
    Leuenroth, S., P. Grutkoski, A. Ayala, and H. Simms. 2000. Suppression of PMN apoptosis by hypoxia is dependent on Mcl-1 and MAPK activity. Surgery. 128(2):171–177.Google Scholar
  30. 30.
    Murakami, M., R. Matsumoto, K. F. Austen, and J. P. Arm. 1994. Prostaglandin endoperoxide synthase-1 and-2 couple to different transmembrane stimuli to generate prostaglandin D2 in mouse bone marrow-derived mast cells. J. Biol. Chem. 269(35):22269–22275.Google Scholar
  31. 31.
    Ray, A. and K. E. Prefontaine. 1994. Physical association and functional antagonism between the p65 subunit of transcription factor NF-kappa B and the glucocorticoid receptor. Proc. Natl.Acad. Sci. USA. 91(2):752–756.Google Scholar
  32. 32.
    Cahen, P., A. C. Kirby, S. R. Porter, and I. Olsen. 2000. Regulation of LFA-3 (CD58) by dexamethasone and retinoic acids in vitro.Inflamm. Res. 49(7):338–344.Google Scholar
  33. 33.
    Cox, G. and R. C. Austin. 1997. Dexamethasone-induced suppression of apoptosis in human neutrophils requires continuous stimulation of new protein synthesis. J. Leukoc. Biol. 61(2):224–230.Google Scholar
  34. 34.
    Sampson, A. 2000. The role of eosinophils and neutrophils in inflammation. Clin. Exp. Allergy. 30(Suppl 1):22–27.Google Scholar
  35. 35.
    Stankova, J., S. Turcotte, J. Harris, M. Rola-Pleszczynski. 2002.Modulation of leukocyte B4 receptor-1 expression by dexamethasone: potential mechanism for enhanced neutrophil survival. J.Immunol. 168(7):3570–3576.Google Scholar

Copyright information

© Plenum Publishing Corporation 2002

Authors and Affiliations

  • Lina M. Ruiz
    • 1
  • Gabriel Bedoya
    • 2
  • James Salazar
    • 3
  • Diana García de O
    • 1
  • Pablo J. Patiño
    • 1
  1. 1.Group of Primary Immunodeficiencies, School of MedicineUniversity of AntioquiaMedellinColombia
  2. 2.Group of Molecular Genetics, School of MedicineUniversity of AntioquiaMedellinColombia
  3. 3.Institute of BiologyUniversity of AntioquiaMedellinColombia

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