Platelet-Activating Factor and Angiogenesis

  • G. Camussi
  • G. Montrucchio
  • E. Lupia
  • M. Arese
  • F. Bussolino
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 416)


Platelet-activating factor (PAF) is a phospholipid autacoid with a spectrum of diverse and potent biological properties relevant for the development of inflammatory reaction and septic shock1. Recently, PAF has been also implicated in the embryogenesis and cell differentiation2,3. Researchers believe that PAF is a mediator of cell to cell communication which may function both as intercellular and intracellular messenger. Since PAF is produced after appropriate stimulation by many cell types, including most inflammatory cells, it has been implicated in the pathogenesis of a variety of diseases4. Moreover, human endothelial cells (EC) were found to produce PAF after stimulation by several inflammatory mediators5,6. Many cell types that synthesized PAF, including EC, are also target for PAF7,8 and express PAF-binding sites on their surface9. PAF, indeed, directly stimulates the endothelium, as it enhances the permeability of EC monolayer and induces changes of the cell cytoskeleton, leading to cell retraction and formation of intercellular gaps8. Moreover, it was observed that, in sub-confluent EC cultures, the redistribution of cytoskeleton was characteristic of cells undergoing translational movements8. These observations prompted us to evaluate whether PAF may stimulate the migration of EC in vitro.


Hepatocyte Growth Factor Platelet Activate Factor Human Endothelial Cell Endothelial Cell Migration Angiogenic Effect 
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.
    Snyder, F. 1990. Platelet-activating factor and related acetylated lipids as potent biological acting cellular mediators. Am. J. Physiol. 259: 697.Google Scholar
  2. 2.
    Leidenheimer, N.J., M.D. Browning, and R.A. Harris. 1991. A physiological role for PAF in the stimulation of mammalian embryonic development. TIPS 12: 82.Google Scholar
  3. 3.
    Bussolino, F., G. Pescarmona, G. Camussi, and F. Gremo. 1988. Acetylcholine and dopamine promote the production of platelet activating factor in immature cells of chick embryonic retina. J. Neurochemistry 51: 1755.CrossRefGoogle Scholar
  4. 4.
    Bratton, D., and P.M. Henson. Cellular origin of PAF. 1989. In: Platelet-activating factor and human diseases. P.J. Barnes, C.P. Page, and P.M. Henson, eds. Blackwell Scientific Publications, London, UK, p. 23.Google Scholar
  5. 5.
    Camussi, G., M. Aglietta, F. Malavasi, C. Tetta, W. Piacibello, F. Sanavio, and F. Bussolino. 1983. The release of platelet-activating factor from human endothelial cells in culture. J. Immunol. 131: 2397.PubMedGoogle Scholar
  6. 6.
    Prescott, S.M., G.A. Zimmerman, and T.M. McIntyre. 1984. Human endothelial cells in culture produce platelet-activating factor (1-alkyl-2-acetyl-sn-glycero-3-phosphocholine) when stimulated with thrombin. Proc. Natl. Acad. Sci. USA 81: 3534.PubMedCrossRefGoogle Scholar
  7. 7.
    Lerner, R., P. Lindstrom, and J. Palmblad. 1988. Platelet activating factor and leukotriene B4 induce hyper-polarization of human endothelial cells but depolarization of neutrophils. Biochem. Biophys. Res. Comm. 153: 805.PubMedCrossRefGoogle Scholar
  8. 8.
    Bussolino, F., G. Camussi, M. Aglietta, M. Braquet, P. Bosia, G. Pescarmona, F. Sanavio, M. D’Urso, and M. Marchisio. 1987. Human endothelial cells are target for platelet-activating factor. 1. Platelet-activating factor induces changes in cytoskeleton structure and promotes albumin diffusion across endothelial mono-layer. J. Immunol. 139: 2439.PubMedGoogle Scholar
  9. 9.
    Korth. R., M. Hirafuji, C. Lalau Keraly, D. Delautier, J. Bidault, and J. Benveniste. 1989. Interaction of the antagonist WEB 2086 and its hetrazepine analogue with human platelets and endothelial cells. Biochem. Pharmacol. 44: 223.Google Scholar
  10. 10.
    Camussi G, Montrucchio G, Lupia E, De Martino A, Perona L, Arese M, Vercellone A, Toniolo A, Buss-solino F. Platelet-activating fcator directly stimulates in vitro migration of endothelial cells and promotes in vivo angiogenesis by an heparin-dependent mechanism. J Immunol 154: 6492–6501, 1995.PubMedGoogle Scholar
  11. 11.
    Folkman, J., and Y. Shing. 1992. Angiogenesis. J. Biol. Chem. 267: 10931.PubMedGoogle Scholar
  12. 12.
    Montrucchio, G., E. Lupia, E. Battaglia, G. Passerini, F. Bussolino, G. Emanuelli, and G. Camussi. 1994. Tumor necrosis factor a-induced angiogenesis depends on in situ platelet-activating factor biosynthesis. J. Exp. Med. 180: 377.PubMedCrossRefGoogle Scholar
  13. 13.
    Andrade, S.P., L.B.G.B. Vieira, Y.S. Bakhle, and P.J. Piper. 1994. Effect of platelet activating (PAF) on the formation of blood vessels in subcutaneous implants in mice. J. Lipid. Mediat. 9: 117Google Scholar
  14. 14.
    Andrade, S.P., L.B.G.B. Vieira, Y.S. Bakhle, and P.J. Piper. 1992. Effects of platelet activating factor (PAF) and other vasoconstrictors on a model of angiogenesis in the mouse. Int. J. Exp. Path. 73: 503.Google Scholar
  15. 15.
    Azizkhan, R.G., J. Clifford Azizkhan, B.R. Zetter, and J. Folkman. 1980. Mast cell heparin stimulates migration of capillary endothelial cells in vitro. J. Exp. Med. 152: 931.PubMedCrossRefGoogle Scholar
  16. 16.
    Bussolino F, Arese M, Montrucchio G, Barra L, Primo L, Benelli R, Sanavio F, Aglietta M, Ghigo D, RolaPleszczynski M, Bosia A, Albini A, Camussi G. Platelet activating factor produced in vitro by Kaposi-s sarcoma cells induces and sustains in vivo angiogenesis. J Clin Invest 96: 940–952, 1995.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media New York 1996

Authors and Affiliations

  • G. Camussi
    • 1
  • G. Montrucchio
    • 2
  • E. Lupia
    • 2
  • M. Arese
    • 2
  • F. Bussolino
    • 2
  1. 1.Cattedra di Nefrologia, Istituto di Medicina e Sanità Pubblica II Facoltà di MedicinaUniversità di PaviaVareseItaly
  2. 2.Dipartimento di Fisiopatologia Clinica e Dipartimento di Genetica, Biologia e Chimica MedicaUniversità di TorinoTorinoItaly

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