Two Structurally Unrelated PAF Antagonists, BN 52021 and BN 52111, Partially Inhibit TNF-Induced Superoxide Release by Human Neutrophils

  • Monique Paubert-Braquet
  • David Hosford
  • Philipe Koltz
  • Jean Guilbaud
  • Pierre Braquet
Part of the NATO ASI Series book series (NSSA, volume 189)


The normal bactericidal response of human neutrophils (PMN) involves cell stimulation, followed by a respiratory burst which results from the activation of NADPH oxidase. This multicomponent electron transport chain transfers electrons from intracellular NADPH to extra-cellular oxygen, reducing molecular oxygen to superoxide. This latter product is rapidly converted to hydrogen peroxide and toxic free radicals (1). Activated PMN also release lysosomal proteases and adhere to the endothelial surface, the cells of which can be severely damaged by the secretion of these toxic products if the local cytotoxic response escalates into a systemic process. Indeed, the microvascular collapse, characterisic of pathologies such as shock, asthma, ischemia and graft rejection, may be partially mediated by dysregulation of PMN functions.


Human Neutrophil Superoxide Production Tumour Necrosis Factor Production Superoxide Release Intracellular NADPH 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    H.L. Malech, and J.I. Gallin, 1987, Neutrophils in human diseases. New Eng J Med. 11: 687.CrossRefGoogle Scholar
  2. 2.
    P. Braquet, L. Touqui, T.S. Shen, and B.B. Vargaftig, 1987, Perspectives in platelet-activating factor research. Pharmacol Reviews. 39:97.Google Scholar
  3. 3.
    A. Cerami, and B. Beutler, 1988, The role of cachectin/TNF in endotoxic shock and cachexia. Immunology Today. 9: 28.Google Scholar
  4. 4.
    K.J. Tracey, B. Beutler, S.F. Lowry, J. Merryweather, S. Wolpe, I.W. Milsark, R.J. Hariri, T.J. Fahey, A. Zentella, J.D. Albert, T. Shires, and A. Cerami, 1986, Shock and tissue injury induced by recombinant human cachectin. Science. 234: 4704.Google Scholar
  5. 5.
    Y. Ozaki, T. Ohashi, Y. Niwa, and S. Kume, S., 1988, Effect of recombinant DNA-produced tumour necrosis factor on various parameters of neutrophil function. Inflammation. 12: 297.Google Scholar
  6. 6.
    G. Camussi, F. Bussolino, G. Salvidio, and C. Baglioni, 1987, Tumour necrosis factor/cachectin stimulates peritoneal macrophages, polymorphonuclear neutrophils, and vascular endothelial cells to synthesize and release platelet-activating factor. J Exp Med. 166:1390.Google Scholar
  7. 7.
    B. Bonavida, J.M. Mencia-Huerta, and P. Braquet, 1989, Effect of platelet-activating factor (PAF) on monocyte activation and production of tumour necrosis factor (TNF). Int Arch Allergy Appl Immunol. 88: 157.PubMedGoogle Scholar
  8. 8.
    G.M. Vercellotti, H.Q. Yin, K.S. Gustafson, P.O. Nelson, H.S. Jacob, 1988, Platelet activating factor primes neutrophil responses to agonists: role in promoting neutrophil-mediated endothelial damage. Blood. 71: 1100.Google Scholar
  9. 9.
    R.L. Berkow, D. Wang, J.W. Larrich, R.W. Dodson, and T.H. Howard, 1987, Enhancement of human neutrophil superoxide production by preincubation with recombinant tumour necrosis factor. J. Immunol. 139:3783.Google Scholar
  10. 10.
    P. Braquet, 1987, The Ginkgolides: potent platelet-activating factor antagonists isolated from Ginkgo Biloba L. Drugs of the Future 12: 643.Google Scholar
  11. 11.
    C. Broquet, and P. Braquet, 1988, Compositions thérapeutiques à base de nouveaux aminoacylates d’acétal du glycerol. Fr. Patent. N° 2.616.326.Google Scholar
  12. 12.
    F.H. Valone, and L.B. Epstein, 1988, Biphasic platelet-activating factor synthesis by human monocytes stimulated with interleukin 1 beta (IL 1), tumor necrosis factor (TNF) or gamma interferon (IFN). J. Immunol. 11:3945.Google Scholar
  13. 13.
    M. Rola-Pleszczynski, 1988, Priming of human monocytes with PAF augments their production of tumour necrosis factor in response to interleukin 1. J. Lipid Mediators. in press.Google Scholar
  14. 14.
    X. Sun, and W. Hsueh, 1988, Bowel necrosis induced by tumor necrosis factor in rats is mediated by platelet-activating factor. J Clin Invest. 81: 1328.Google Scholar
  15. 15.
    M.L. Blank, T.C. Lee, V. Fitzgerald, and F. Snyder, 1981, Anti-hypertensive activity of an alkyl ether analog of phosphatidylcholine. Biochem. Biophys. Res. Commun. 29: 2472.Google Scholar
  16. 16.
    H. Heuer, and G. Letts, 1989, Priming of effects of PAF in vivo by tumor necrosis factor and endotoxin. J. Lipid Mediators. in press.Google Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Monique Paubert-Braquet
    • 1
  • David Hosford
    • 2
  • Philipe Koltz
    • 1
  • Jean Guilbaud
    • 1
  • Pierre Braquet
    • 2
  1. 1.Burn CentreClamartFrance
  2. 2.IHBLe Plessis-RobinsonFrance

Personalised recommendations