Neutrophil-induced Oxidative Stress

  • M. Lamy
  • M. Mathy-Hartert
  • G. Deby-Dupont
Conference paper
Part of the Yearbook of Intensive Care and Emergency Medicine book series (YEARBOOK, volume 1996)


The respiratory burst of neutrophils, as well as their degranulation, constitutes a defensive response to tissue damage, whether induced by mechanical, chemical, or infectious stimuli [1]. This response, which is normally tightly regulated, leads to leukocyte migration into the area of damage [2]. Macrophages, polymorphonuclear neutrophils (PMN), and lymphocytes are recruited and stimulated, with concomitant production of soluble mediators (cytokines, prostanoids, leukotrienes, acute phase reactant proteins, etc.). This response is beneficial for the organism, because it leads to the phagocytosis of microorganisms and foreign material, lysis within phagolysosomes, and production of antibodies by lymphocytes. The vascular endothelium is also involved in this beneficial response, because local inflammation is associated with vasodilation and diapedesis of neutrophils across the vascular wall into the inflammatory focus. Specific receptors, both on the neutrophils and the endothelial cells play an important role in any inflammatory process [3–6].


Singlet Oxygen Systemic Inflammatory Response Syndrome Human Endothelial Cell Respiratory Burst Multiple Organ Dysfunction Syndrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Klebanoff SJ (1988) Phagocytic cells: Products of oxygen metabolism. In: Gallin JI, Goldstein IM, Snyderman R (eds) Inflammation, basic principles and clinical correlates. Raven Press, New York, pp 391–444Google Scholar
  2. 2.
    Malech HL (1988) Phagocytic cells: Egress grom marrow and diapedesis. In: Gallin JJ, Goldstein IM, Snyderman R (eds) Inflammation, basic principles and clinical correlates. Raven Press, New York, pp 297–308Google Scholar
  3. 3.
    Pober JS, Cotran RS (1990) The role of endothelial cells in inflammation. Transplantation 50: 537–544PubMedCrossRefGoogle Scholar
  4. 4.
    Zimmerman GA, Prescott SM, Mcintyre TM (1992) Endothelial cell interactions with granulocytes: Tethering and signaling molecules. Immunology Today 13: 93–99PubMedCrossRefGoogle Scholar
  5. 5.
    Williams TJ, Hellewell PG (1992) Endothelial cell biology: Adhesion molecules involved in the microvascular inflammatory response. Am Rev Respir Dis 146: 545–550Google Scholar
  6. 6.
    Gee MH, Albertine KH (1993) Neutrophil-endothelial cell interactions in the lung. Ann Rev Physiol 55: 227–248CrossRefGoogle Scholar
  7. 7.
    Weiss SJ (1989) Tissue destruction by neutrophils. New Engl J Med 320: 365–376PubMedCrossRefGoogle Scholar
  8. 8.
    Fujishima S, Aikawa N (1995) Neutrophil-mediated tissue injury and its modulation. Intensive Care Med 21: 277–285PubMedCrossRefGoogle Scholar
  9. 9.
    Thommasen HV, Boyko WJ, Runell JA, Hogg JC (1984) Transient leucopenia associated with adult respiratory distress syndrome. Lancet 1: 809–812PubMedCrossRefGoogle Scholar
  10. 10.
    Neuhof H (1991) Actions and interactions of mediator systems and mediators in the pathogenesis of ARDS and multiorgan failure. Acta Anaesthesiol Scand 35 (suppl 95) : 7–14CrossRefGoogle Scholar
  11. 11.
    Tagan M, Markert M, Schaller M, Feihl F, Chiolero R, Perret C (1991) Oxidative metabolism of circulating granulocytes in adult respiratory distress syndrome. Am J Med 91 (suppl 3c): 72S-78SPubMedCrossRefGoogle Scholar
  12. 12.
    Oddel EW, Segal A W (1988) The bactericidal effects of the respiratory burst and the myeloperoxidase system isolated in neutrophil cytoplasts. Biochim Biophys Acta 971: 266–274CrossRefGoogle Scholar
  13. 13.
    Deby C, Goutier R (1990) New perspectives on the biochemistry of superoxide anion and the efficiency of superoxide dismutases. Biochem Pharmacol 39: 399–405PubMedCrossRefGoogle Scholar
  14. 14.
    Deby C, Hartstein G, Deby-Dupont G, Lamy M (1995) Antioxidant therapy. In: Bion JF, Burchardi H, Dellinger RP, Dobb GJ (eds) Current topics in intensive care n°2, W.B. Saunders, London, pp 175–205Google Scholar
  15. 15.
    Klebanoff SJ, Hamon CB (1972) Role of myeloperoxidase-mediated antimicrobial systems in intact leukocytes. J Reticuloendothel Soc 12: 170–196PubMedGoogle Scholar
  16. 16.
    Weiss SJ, Lampert MB, Test ST (1983) Long-lived oxidants generated by human neutrophils: Characterization and bioactivity. Science 222: 625–628PubMedCrossRefGoogle Scholar
  17. 17.
    Grisham MB, Jefferson MM, Melton DF, Thomas EL (1984) Chlorination of endogenous amines by isolated neutrophils. J Biol Chern 259: 10404–10413Google Scholar
  18. 18.
    Matheson NR, Wong PS, Travis J (1979) Enzymatic inactivation of human α1-proteinase inhibitor. Biochem Biophys Res Comm 88: 402–409PubMedCrossRefGoogle Scholar
  19. 19.
    Reddy VY, Pizzo SV, Weiss SJ (1989) Functional inactivation and structural disruption of human az-macroglobulin by neutrophils and eosinophils. J Biol Chern 264: 13801–13809Google Scholar
  20. 20.
    Deby-Dupont G, Croisier JL, Camus G, et al (1994) Inactivation of a2-macroglobulin by activated human polymorphonuclear leukocytes. Mediators of Inflammation 3: 117–123PubMedCrossRefGoogle Scholar
  21. 21.
    Allen RC, Stjernholm RL, Streele RH (1972) Evidence for the generation of an electronic excitation state(s) in human polymorphonuclear leukocytes and its participation in bactericidal activity. Bioch Biophys Res Commun 47: 679–684CrossRefGoogle Scholar
  22. 22.
    Kanofsky JR (1984) Biochemical requirements for singlet oxygen production by purified human myeloperoxidase. J Clin Invest 74: 1489–1495PubMedCrossRefGoogle Scholar
  23. 23.
    Henson PM, Henson JE, Fittschen C, Kimani G, Bratton DL, Riches DWH (1988) Phagocytic cells: Degranulation and secretion. In: Gatlin JI, Goldstein IM, Snyderman R (eds) Inflammation, basic principles and clinical correlates. Raven Press, New York, pp 363–390Google Scholar
  24. 24.
    Dinarello CA, Gelfand JA, Wolff SM (1993) Anticytokine strategies in the treatment of the systemic inflammatory response syndrome. JAMA 269: 1829–1835PubMedCrossRefGoogle Scholar
  25. 25.
    Donnelly SC, Strieter RM, Kunker SL, et al (1993) Interleukin-8 and development of adult respiratory distress syndrome in at-risk patient groups. Lancet 341 : 643–647PubMedCrossRefGoogle Scholar
  26. 26.
    Osborn L (1990) Leukocyte adhesion to endothelium in inflammation. Cell 62: 3–6PubMedCrossRefGoogle Scholar
  27. 27.
    Moncada S, Palmer R, Higgs E (1991) Nitric oxide: Physiology, pathophysiology and pharmacology. Pharmacol Rev 43: 109–142PubMedGoogle Scholar
  28. 28.
    Jaff EA (1987) Cell biology of endothelial cells. Hum Pathol 18: 234–239CrossRefGoogle Scholar
  29. 29.
    Hynes RO (1987) Integrins: A family of cell surface receptors. Cell 48: 549–554PubMedCrossRefGoogle Scholar
  30. 30.
    Abdelda SM (1991) Endothelial and epithelial cell adhesion molecules. Am J Respir Cell Mol Biol 4: 195–203Google Scholar
  31. 31.
    Beilke MA (1989) Vascular endothelium in immunology and infectious disease. Rev Infect Dis 11: 273–283PubMedCrossRefGoogle Scholar
  32. 32.
    Fisher Jr CJ, Dhainaut JF, Pribble JP, Pharm D, Knaus WA, Thompson RC (1993) The IL-1ra Phase III sepsis syndrome study group. A phase III multicenter trial of human recombinant interleukin-1 receptor antagonist (IL-1ra) in the treatment of patients with sepsis syndrome. Lymphokine Cytokine Res 12: 390–396Google Scholar
  33. 33.
    Mohler KM, Torrance DS, Smith CA, et al (1993) Soluble tumor necrosis factor (TNF) receptors are effective therapeutic agents in lethal endotoxemia and function simultaneously as both TNF carriers and TNF antagonists. J Immunol 151: 1548–1561PubMedGoogle Scholar
  34. 34.
    Wilson E, Elesite MC, Bell RM, Merrill AM, Lambeth JD (1986) Inhibtion of the oxidative burst in human neutrophils by sphingold long-chain bases. J Biol Chern 261: 12616–12623Google Scholar
  35. 35.
    Wilson E, Rice WG, Kinkade JM, Merrill A, Arnold RR, Lambeth JD (1987) Proteinkinase-C inhibition by sphingold long-chain bases: Effects on secretion in human neutrophils. Arch Biochem Biophys 259: 204–214PubMedCrossRefGoogle Scholar
  36. 36.
    Wolff HRD, Seegert HW (1982) Experimental and clinical results in shock lung treatment with vitamine E. Annals NY Acad Sci 393: 392–409CrossRefGoogle Scholar
  37. 37.
    Fukase Y, Abe Y, Takahashi T, Ishikawa M (1989) Effect of antibiotic administration on chemiluminescence and adherence of human neutrophils. Chemotherapy 37: 1195–1199Google Scholar
  38. 38.
    Gunther MR, Mao J, Cohen MS (1993) Oxidant-scavenging activities of ampicillin and sulbactam and their effect on neutrophil functions. Antimicrob Agents Chemother 37: 950–956PubMedGoogle Scholar
  39. 39.
    Ottonello L, Datlegri F, Dapino P, Pastorino G, Sacchetti C (1991) Cytoprotection against neutrophil-delivered oxidant attack by antibiotics. Biochem Pharmacol 42: 2317–2321PubMedCrossRefGoogle Scholar
  40. 40.
    Cantin A, Woodds DE (1993) Protection by antibiotics against myeloperoxidase-dependent cytotoxicity to lung epithelial cells in vitro. J Clin Invest 91: 38–45PubMedCrossRefGoogle Scholar
  41. 41.
    Wasil M, Haliwell B, Moorhouse CP (1988) Scanvenging of hypochlorous acid by tetracycline, rifampicin and some other antibiotics: A possible antioxidant action of rifampicin and tetracycline? Biochem Pharmacol 37: 775–778PubMedCrossRefGoogle Scholar
  42. 42.
    Lapenna D, Cellini I, De Giola S, et al (1995) Cephalosporins are scavengers of hypochlorous acid. Biochem Pharmacol 49: 1249–1254PubMedCrossRefGoogle Scholar
  43. 43.
    Seliger HH (1964) Chemiluminescence of H2O2-NaOCl solutions. J Chern Physics 40: 3133–3134CrossRefGoogle Scholar
  44. 44.
    Khan AU, Kasha M (1970) Chemiluminescence arising from simultaneous transitions in pairs of singlet oxygen molecules. J Am Chern Soc 92: 3293–3300CrossRefGoogle Scholar
  45. 45.
    Cadenas E, Sies H (1984) Low-level chemiluminescence as an indicator of singlet molecular oxygen in biological systems. Meth Enzymol 105: 221–229PubMedCrossRefGoogle Scholar
  46. 46.
    Khan AU (1984) Myeloperoxidase singlet molecular oxygen generation detected by direct infrared electronic emission. Biochem Biophys Res Commun 122: 668–675PubMedCrossRefGoogle Scholar
  47. 47.
    Deby C, Deby-Dupont G, Mathy-Hartert M, et al (1993) Can transition metal chelators act as antioxidant factors by another pathway than metal coordination? The case of ceftazidime. In: Conference on Iron and Microbial Iron Chelates, Bruges, Belgium (Abstr 39)Google Scholar
  48. 48.
    Mathy-Hartert M, Deby C, Deby-Dupont G, Vandenberghe A, Jadoul L, Lamy M (1994) Mechanisms of antioxidant protection of endothelial cells against polymorphonuclear leucocyte oxidant stress by ceftazidime. Clin Intens Care 5 (Suppl 2): 74 (Abst)Google Scholar
  49. 49.
    Deby-Dupont C, Mathy-Hartert M, Jadoul L, Vandenberghe A, Lamy M, Deby C (1994) Ceftazidime: An antibiotic with a host defense spectrum interesting in cases of deleterious polymorphonuclear leukocytes (PMN) activation. In: 34th Interscience Conference on Antimicrobial Agents and Chemotherapy, Orlando, Florida, USA, p 42 (Abstr G30)Google Scholar
  50. 50.
    Mathy-Hartert M, Deby-Dupont G, Deby C, Jadoul L, Vandenberghe A, Lamy M (1995) Effect of ceftazidime on activated oxygen species produced by endiothelial cells and polymorphonuclear leukocytes. In: 35th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, California, p 161 (Abstr GIS)Google Scholar
  51. 51.
    Weiss SJ, Young J, LoBuglio AF, Slivka A, Nimeh NF (1981) Role of hydrogen peroxide in neutrophil-mediated destruction of cultured endothelial cells. J Clin Invest 68: 714–721PubMedCrossRefGoogle Scholar
  52. 52.
    Mathy-Hartert M, Deby-Dupont G, Deby C, Jadoul L, Vandenberghe A, Lamy M (1996) Cytotoxicity induced by neutrophil myeloperoxidase towards human endothelial cells: Protection by ceftazidime. Mediators of Inflammation 4 (In press)Google Scholar
  53. 53.
    Deby-Dupont G, Mathy-Hartert M, Deby C, Jadoul L, Vandenberghe A, Lamy M (1995) Ceftazidime (CAZ) protects plasmatic antiproteases from oxidative inactivation. Can J Infect Dis 6 (Suppl C): 425C (Abst)Google Scholar
  54. 54.
    Rains CP, Bryson HM, Peters DH (1995) Ceftazidime. An update of its antibacterial activity, pharmacokinetic properties and therapeutic effect. Drugs 49: 577–617PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1996

Authors and Affiliations

  • M. Lamy
  • M. Mathy-Hartert
  • G. Deby-Dupont

There are no affiliations available

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