Extracellular and Intracellular Activities of PAF

  • Peter M. Henson


The potent and wide-ranging biologic activities of PAF are well documented (see Chapters 11–20). Nevertheless, we still have not determined when and where, in endogenous physiologic and pathologic processes, PAF is actually playing a role. In this chapter, I discuss some of the issues relating to where PAF may act and the nature of its biologic properties. Of necessity, the consideration is somewhat speculative, since the appropriate studies to address these questions are really only in their infancy. Moreover, because of the extensive discussion of the properties of PAF in this book, the references should be considered as illustrative and not exhaustive. Hopefully, the ideas elaborated herein will provide at the minimum an inducement for further investigation. It is even possible that this chapter will provide the beginnings of a framework that can be used to place the ether phospholipids now known as PAF into their proper context in pathophysiologic processes. For this discussion, the term PAF is used generically for molecules with structures and biologic activity similar to, or identical with, hexadecyl acetyl glycerophospho-choline.


Platelet Activate Factor Intracellular Activity Glyceryl Ether Rabbit Platelet Platelet Activate Factor Receptor 
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. Accurso, F. J., Abman, S., Wilkening, R. B., Worthen, S., and Henson, P. M., 1986, Exogenous platelet activating factor produces pulmonary vasodilation in the ovine fetus, Am. Rev. Resp. Dis. 133(Suppl. 4):A11.Google Scholar
  2. Albert, D. H., and Snyder, F., 1984, Release of arachidonic acid from l-alkyl-2-acykv«-glycero-3-phosphocholine, a precursor of platelet-activating factor, in rat alveolar macrophages, Biochem. Biophys. Acta 796:92–101.PubMedGoogle Scholar
  3. Alonso, F., Garcia-Gil, M., Sanchez-Crespo, M., and Mato, J. M., 1982, Activation of l-alkyl-2-lyso-glycero-3-phosphocholine acetyl-CoA transferase during phagocytosis in human polymorphonuclear leukocytes, J. Biol. Chem. 257:3376–3378.PubMedGoogle Scholar
  4. Arnold, B., and Weltzien, H. U., 1976, Effects of a synthetic lysolecithin analog on the phase transition of mixtures of phosphatidylethanolamine and phosphatidylcholine, FEBS Lett. 61(2): 199–202.PubMedCrossRefGoogle Scholar
  5. Benveniste, J., 1986, Comments in New Horizons in Platelet Activating Factor Research (C. M. Winslow and M. C. Lee, eds.), Wiley, New York.Google Scholar
  6. Benveniste, J., Roubin, R., Chignard, M., Jouvin-Marche, E., and LeCouedic, P., 1982, Release of platelet-activating factor (PAF-acether) and 2-lysoPAF-acether from three cell types, Agents Actions 12:711–713.PubMedCrossRefGoogle Scholar
  7. Billah, M. M., and Johnston, J. M., 1983, Identification of phospholipid platelet-activating factor (1–0alkyl-2-acetyl-sn-glycero-3-phosphocholine) in human amniotic fluid and urine, Biochem. Biophys. Res. Commun. 113:51–58.PubMedCrossRefGoogle Scholar
  8. Blank, M. L., Snyder, F., Byers, L. W., Brooks, B., and Muirhead, E. E., 1979, Antihypertensive activity of an alkyl ether analog of phosphatidylcholine, Biochem. Biophys. Res. Commun. 90:1194–2000.PubMedCrossRefGoogle Scholar
  9. Blank, M. L., Cress, E. A., Lee, T.-C., Malone, B., Surles, J. R., Piantadosi, C., Hajdu, J., and Snyder, F., 1982, Structural features of platelet activating factor (l-alkyl-2-acetyl-sn-glycero-3phosphocholine) required for hypotensive and platelet serotonin responses, Res. Commun. Chem. Pathol. Pharmacol. 38:3–20.PubMedGoogle Scholar
  10. Bussolino, F., Gremo, F., Tetta, C., Pescarmona, G. P., and Camussi, G., 1986, Production of platelet activating factor by chick retina, J. Biol. Chem. 261:16502–16508.PubMedGoogle Scholar
  11. Chang, S., Fedderson, O., Worthen, G. S., Henson, P. M., and Voelkel, N., 1986, CV3988, a PAF antagonist and ethanol protect against endotoxin-induced hemodynamic alterations in rat, in: New Horizons in Platelet Activating Factor Research (C. M. Winslow and M. L. Lee, eds.), Wiley, New York, pp. 293–301.Google Scholar
  12. Chenoweth, D. E., and Hugh, T. E., 1978, Demonstration of specific C5a receptor on intact human polymorphonuclear leukocytes, Proc. Natl. Acad. Sci. USA 75:3943–3947.PubMedCrossRefGoogle Scholar
  13. Chesney, C. M., Pifer, D. O., and Hugh, K. M., 1985, Desensitization of human platelets by platelet activating factor, Biochem. Biophys. Res. Commun. 127:24–30.PubMedCrossRefGoogle Scholar
  14. Chilton, F. H., and Murphy, R. C, 1986, Remodeling of arachidonate-containing phosphoglycerides within the human neutrophil, J. Biol. Chem. 261:7771–7777.PubMedGoogle Scholar
  15. Clay, K. F., and Baker, R. C, 1985, Determination of platelet activating factor in mouse brain tissue. Proceedings of the 33rd Annual Conference on Mass Spectrometry and Allied Topics, pp. 700– 701, A.Google Scholar
  16. Cox, C. P., Wardlow, M. C., Jorgensen, R., and Farr, R. S., 1981, The presence of platelet activating factor (PAF) in normal human mixed saliva, J. Immunol. 127:46–50.PubMedGoogle Scholar
  17. Goetzl, E. J., Derian, C. K., Tauber, A. I., and Valone, F. H., 1980, Novel effects of l-O-hexadecyl-2acyl-srt-glycero-3-phosphorylcholine mediators on human leukocyte function: Delineation of the specific roles of the acyl substituents, Biochem. Biophys. Res. Commun. 94:881–888.PubMedCrossRefGoogle Scholar
  18. Gomez-Cambronero, J., Dieto, M. L., Mato, J. M., and Sanchez-Crespo, M., 1985a, Modulation of lyso-platelet-activating factor : acetyl-CoA acetyl transferase from rat splenic microsomes. The role of calcium ions, Biochem. Biophys. Acta 845:511–515.PubMedCrossRefGoogle Scholar
  19. Gomez-Cambronero, J., Velasco, S., Mato, J. M., Sanchez-Crespo, M., 1985b, Modulation of lysoplatelet activating factor : acetyl-CoA acetyl transferase from rat splenic microsomes. The role of cyclicAMP-dependent protein kinase, Biochem. Biophys. Acta 845:516–519.PubMedCrossRefGoogle Scholar
  20. Grandel, K. E., Farr, R. S., Wanderer, A. A., Sisenstadt, T. C., and Wasserman, S. I., 1985, Association of platelet-activating factor with primary acquired cold urticaria, N. Engl. J. Med. 313:405–409.PubMedCrossRefGoogle Scholar
  21. Hadvary, P., and Baumgartner, H. R., 1983, Activation of human and rabbit blood platelets by synthetic structural analogs of platelet activating factor, Thrombosis Res. 30:143–156.CrossRefGoogle Scholar
  22. Harris, R. A., Clay, K., Murphy, R., and Henson, P., 1985, Effects of PAF and related lipids on membrane physical properties, Fed. Proc. 44:858.Google Scholar
  23. Henson, P. M., 1971, The immunologic release of constituents from neutrophil leukocytes. II. Mechanisms of release during phagocytosis, and adherence to nonphagcytosable surfaces, J. Immunol. 107:1547–1557.PubMedGoogle Scholar
  24. Henson, P. M., 1976, Activation and desensitization of platelets by platelet activating factor (PAF) derived from IgE-sensitized basophils. I. Characteristics of the secretory response, J. Exp. Med. 143:937–952.PubMedCrossRefGoogle Scholar
  25. Henson, P. M., and Pinckard, R. N., 1977, Basophil derived platelet activating factor (PAF) as an in vivo mediator of acute allergic reactions. Demonstration of specific desensitization of platelets to PAF during IgE-induced anaphylaxis in the rabbit, J. Immunol. 119:2179–2184.PubMedGoogle Scholar
  26. Hwang, S., Lam, M., and Pong, S., 1986, Ionic and GTP regulation of binding of platelet-activating factor to receptors and platelet-activating factor-induced activation of GTPase in rabbit platelet membranes, J. Biol. Chem. 261(2):532–537.PubMedGoogle Scholar
  27. Hwang, S.-B., Lee, C.-S., C., Cheah. M. J., and Shen, T. Y., 1983. Specific receptor sites for 1–0alkyl-2–0-acetyl-sn-glycero-3-phosphocholine (platelet activating factor) on rabbit platelet and guinea pig smooth muscle membranes, Biochemistry 22:4756–4763.PubMedCrossRefGoogle Scholar
  28. Jain, M. K., and DeHaas. G. H., 1985, Activation of phospholipase A2 by freshly added lysophospholipids, Biochem. Biophys. Acta 736:157–162.Google Scholar
  29. Keraly, C. L., and Benveniste. J., 1982, Specific desensitization of rabbit platelets by platelet activating factor (Paf-acether) and derivatives, Br. J. Haematol. 51:313–322.PubMedGoogle Scholar
  30. Klopfenstein, W. E., deKruyff, B., Verkleij, A. J., andDemel, R. A., and vanDeenen, L. L. M., 1974, Differential scanning calorimetry on mixtures of lecithin, lysolecithin and cholesterol. Chem. Phys. Lipids 13:215–222.CrossRefGoogle Scholar
  31. Krilis, S., Lewis, R. A., Corey, E. J., and Austen, K. F., 1983, Specific receptors for leukotriene C4 on a smooth muscle cell line, J. Clin. Invest. 72:1516–1519.PubMedCrossRefGoogle Scholar
  32. Krilis, S., Lewis, R. A., Corey, E. J., and Austen. K. F., 1984, Specific binding of leukotriene C4 to ileal segments and subcellular fractions of ileal smooth muscle cells, Proc. Natl. Acad. Sci. USA 81:4529–4533.PubMedCrossRefGoogle Scholar
  33. Kumar, R., King, R. J., and Hanahan, D. J., 1986, Processing of platelet activating factor (PAF) by interstitial and epithelial cells from rat lungs, in: New Horizons in Platelet Activating Factor Research (C. M. Winslow and M. L. Lee, eds.), Wiley, Chichester, pp. 97–102.Google Scholar
  34. Lambrecht, G., and Parnham, M. J., 1986, Kadsurenone distinguishes between different platelet activating factor receptor subtypes on macrophages and polymorphonuclear leucocytes, Br. J. Pharmacol. 87:287–289.PubMedGoogle Scholar
  35. Lee, T.-C., 1985, Biosynthesis of platelet activating factor. Substrate specificity of l-alkyl-2-lyso-snglycero-3-phosphocholine : acetyl-CoA acetyltransferase in rat spleen microsomes, J. Biol. Chem. 260:10952–10955.PubMedGoogle Scholar
  36. Leslie, C. C., and Detty, D. M., 1986, Arachidonic acid turnover in response to lipopolysaccharide and opsonized zymosan in human monocyte-derived macrophages, Biochem. J. 236:251–259.PubMedGoogle Scholar
  37. Ludwig, J. C., Hoppens, C. L., McManus, L. M., Mott, G. E., and Pinckard, R. N., 1985, Modulation of platelet-activating factor (PAF) synthesis and release from human polymorphonuclear leukocytes (PMN): Role of extracellular albumin, Arch. Biochem. Biophys. 241:337–347.PubMedCrossRefGoogle Scholar
  38. Ludwig, J. C., McManus, L. M., Clark, P. D., Hanahan, D. J., and Pinckard, R. N., 1984, Modulation of platelet-activating factor (PAF) synthesis and release from human polymorphonuclear leukocytes (PMN): Role of extracellular calcium, Arch. Biochem. Biophys. 232:102–110.PubMedCrossRefGoogle Scholar
  39. Lumb, R. H., Pool, G. L., Bubacz, D. G., Blank, M. L., and Snyder, F., 1983, Spontaneous and protein-catalyzed transfer of l-alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet-activating factor) between phospholipid bilayers, Biochem. Biophys. Acta 750:217–222.PubMedGoogle Scholar
  40. Lynch, J. M., and Henson, P. M., 1986, The intracellular retention of newly synthesised platelet activating factor, J. Immunol. 137:2653–2661.PubMedGoogle Scholar
  41. Lynch, J. M., Spears, P., and Henson, P. M., 1982, The specific inhibition of platelet activating factor (PAF) stimulation of rabbi rabbit platelets by a monoclonal antiplatelet antibody, Fed. Proc. 41:528.Google Scholar
  42. Mallet, A. I., and Cunningham, F. M., 1985, Structural identification of platelet activating factor in psoriatic scale, Biochem. Biophys. Res. Commun. 126:192–198.PubMedCrossRefGoogle Scholar
  43. Mangold, H. K., and Paltauf, F. (eds.), 1983, Ether Lipids. Biochemical and Biomedical Aspects, Academic Press, New York.Google Scholar
  44. McMurtry, I. F., Morris, K. G., 1986, Platelet activating factor causes pulmonary vasodilation in the rat, Am. Rev. Respir. Dis. 134:757–762.PubMedGoogle Scholar
  45. Murphy, R. C., and Henson, P. M., 1985, Mediator network, Ann. Inst. Pasteur/Immunol. 136D:175– 228.Google Scholar
  46. Neufeld, E. J., Majerus, P. W., Krueger, C. M., and Saffitz, J. E., 1985, Uptake and subcellular distribution of (3H) arachidonic acid in murine fibrosarcoma cells measured by electron microscope autoradiography, J. Cell Biol. 101:573.PubMedCrossRefGoogle Scholar
  47. Ninio, E., 1986, Regulation of PAF-acether biosynthesis in different cell types, in: New Horizons in Platelet Activating Factor Research (C. M. Winslow and M. L. Lee, eds.), Wiley, New York.Google Scholar
  48. O’Flaherty, J. T., Lees, C. J., Miller, C. H., McCall, C. E., Lewis, J. C., Love, S. H., and Wykle, R. L., 1981, Selective desensitization of neutrophils: Further studies with l-O-alkyl-srt-glycero-3phosphocholine analogues, J. Immunol. 127:731–737.PubMedGoogle Scholar
  49. O’Flaherty, J. T., Surles, J. R., Redman, J., Jacobson, D., Piantadosi, C., Wykle, R. L., 1986, Binding and metabolism of platelet activating factor by human neutrophils, J. Clin. Invest. 78:381–388.PubMedCrossRefGoogle Scholar
  50. Pinckard, R. N., Farr, R. S., and Hanahan, D. J., 1979, Physiochemical and functional identification of rabbit platelet activating factor (PAF) released in vivo during IgE anaphylaxis with PAF released in vitro from IgE-sensitive basophils, J. Immunol. 123:1847–1857.PubMedGoogle Scholar
  51. Riches, D. W. H., Young, S. K., Seccombe, J. F., Lynch, J. M., and Henson, P. M., 1985, The subcellular distribution of platelet-activating factor (PAF) in phagocytosing human neutrophils, Fed. Proc. 44:137.Google Scholar
  52. Roubin, R., Mencia-Huerta, J.-M., and Benveniste, J., 1982, Release of platelet-activating factor (Pafacether) and leukotrienes C and D from inflammatory macrophages, Eur. J. Immunol. 12:141–146.PubMedCrossRefGoogle Scholar
  53. Sanchez-Crespo, M., Inarrea, P., Alvarez, V., Alonso, F., Egido, J., and Hernando, L., 1983, Presence in normal human urine of a hypotensive and platelet-activating phospholipid, Am. J. Physiol. 244:F706–F711.PubMedGoogle Scholar
  54. Satouchi, K., Pinckard, R. N., McManus, L. M., and Hanahan, D. J., 1981, Modification of the polar head group of acetyl glyceryl ether phosphoryl choline and subsequent effects upon platelet activation, J. Biol. Chem. 256:4425–4432.PubMedGoogle Scholar
  55. Shaw, J. O., and Henson, P. M., 1980, The binding of rabbit basophil-derived platelet activating factor to rabbit platelets, Am. J. Pathol. 98:791–810.PubMedGoogle Scholar
  56. Shen, T. Y., Hwang, S. B., Cheah, M. J., and Lee, C.-S. C., 1983, Effects of nonsteroidal antiinflam matory drugs on the specific binding of platelet-activating factor to membrane preparations of rabbit platelets, in: Platelet-Activating Factor and Structurally Related Ether Lipids (J. Benveniste and B. Arnoux, eds.), Elsevier Science Publishers, Amsterdam, pp. 167–176.Google Scholar
  57. Snyder, F., 1986, The significance of dual pathwavs for the biosynthesis of platelet activating factor: Alkyl acetyl glycerols and lyso-PAF as immediate precursors, in: New Horizons in Platelet Activating Factor Research (C. M. Winslow and M. L. Lee, eds.), Wiley, New York, pp. 13–25.Google Scholar
  58. Snyderman, R., Pike, M. C., Edge, S., and Lane, B., 1984, A chemoattractant receptor on macrophages exists in two affinity states regulated by guanine nucleotides, J. Cell Biol. 98:444–448.PubMedCrossRefGoogle Scholar
  59. Stenmark, K., Eyzaguirre, R., Remigio, L., Seccombe, J., and Henson, P. M., 1985, Recovery of platelet activating factor and leukotrienes from infants with severe bronchopulmonary dysplasia: Clinical improvement with cromolyn treatment, Am. Rev. Resp. 131:A236.Google Scholar
  60. Stimler, N., Parasympathetic stimulation as a mechanism for PAF-induced contractile responses in lung, in: New Horizons in Platelet Activating Factor Research (C.M. Winslow and M. L. Lee, eds.), Wiley, Chichester, pp. 269–275.Google Scholar
  61. Valone, F. H., 1984, Isolation of a platelet membrane protein which binds the platelet-activating factor l-0-hexadecyl-2-acetyl-sn-glycero-3-phosphorylcholine, Immunology 52:169–174.PubMedGoogle Scholar
  62. Valone, F. H., Coles, E., Reinhold, V. R., and Goetzl, E. J., 1982, Specific binding of phospholipid platelet-activating factor by human platelets, J. Immunol. 129:1637–1641.PubMedGoogle Scholar
  63. VanEchteld, C. J. A., DeKruiff, B., and DeGier, J., 1980, Differential miscibility properties of various phosphatidylcholine/lysophosphatidylcholine mixtures, Biochem. Biophys. Acta 595:71–81.CrossRefGoogle Scholar
  64. Voelkel, N. F., Chang, S., Worthen, G. S., McMurtry, I., and Henson, P. M., 1986, PAF antagonists:Different effects on platelets, neutrophils, guinea pig ileum and PAF-induced vasodilation in isolated rat lung, Prostaglandins 32(3):359–372.PubMedCrossRefGoogle Scholar
  65. Weltzien, H. U., 1979, Cytolytic and membrane-perturbing properties of lysophosphatidylcholine, Biochem. Biophys. Acta 559:259–287.PubMedGoogle Scholar
  66. Wykle, R. L., Miller, C. H., Lewis, J. C., Schmitt, J. D., Smith, J. A., Surles, J. R., Piantadosi, C.,and O’Flaherty, J. T., 1981, Stereospecific activity of l-0-alkyl-2-O-acetyl-sn-glycero-3-phosphocholine and comparison of analogs in the degranulation of platelets and neutrophils, Biochem. Biophys. Res. Commim. 100:1651–1658.CrossRefGoogle Scholar
  67. Zilversmit, D. B., 1984, Lipid transfer proteins, J. Lipid Res. 25:1563–1569.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Peter M. Henson
    • 1
  1. 1.National Jewish Center for Immunology and Respiratory MedicineDenverUSA

Personalised recommendations