Platelet-Activating Factor Amplifies Tumour Necrosis Factor-Induced Superoxide Generation by Human Neutrophils

  • Monique Paubert-Braquet
  • Philipe Koltz
  • Jean Guilbaud
  • David Hosford
  • Pierre Braquet
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 264)


Inflammation is usually a tightly controlled process which confines tissue damage, prevents infection and assists in cellular regeneration. However, if the inflammatory response becomes unregulated, this normally beneficial local event may escalate into a wider malignant activity involving endothelial injury, excessive cell infiltration and vascular leakage. Such phenomena may underlie the microcirculatory damage observed in shock, sepsis, asthma, ischemia and graft rejection. Neutrophils (PMN) appear to play a particularly important role in inflammation and inflammatory disorders (1). In the inflammatory microenvironment, neutrophils become activated by various agonists, adhere to the endothelial surface and release lysosomal proteases. Activated PMN also undergo a “respiratory burst”, which results in the reduction of molecular oxygen to superoxide (1). These toxic products released by PMN are capable of eliciting severe endothelial damage.


Superoxide Production Superoxide Generation Tumour Necrosis Factor Production Superoxide Release Tumour Necrosis Factor Concentration 


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.PubMedCrossRefGoogle 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.CrossRefGoogle Scholar
  5. 5.
    Y. Ozaki, T. Ohashi, Y. Niwa, and S. Kume, 1988, Effect of recombinant DNA-produced tumour necrosis factor on various parameters of neutrophil function. Inflammation., 12:297.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedGoogle 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.PubMedGoogle 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 dacétal du glycerol. Fr. Patent. Nº 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.PubMedCrossRefGoogle 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
  • Philipe Koltz
    • 1
  • Jean Guilbaud
    • 1
  • David Hosford
    • 2
  • Pierre Braquet
    • 2
  1. 1.Burn CentreH.I.A. PercyClamartFrance
  2. 2.IHBLe Plessis-RobinsonFrance

Personalised recommendations