Agents and Actions

, Volume 11, Issue 6–7, pp 556–558 | Cite as

Is platelet-activating factor (PAF-acether) synthesis by murine peritoneal cells (PC) a two-step process?

  • Jean Michel Mencia-Huerta
  • Ewa Ninio
  • Régine Roubin
  • Jacques Benveniste
Proceedings of the 3rd European Workshop on Inflammation, Paris, 2–3 March 1981 Phospholipase: Role in Cellular Activation


PAF-acether (1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine) is released from several cell sources simultaneously with an inactive non-acylated compound (1-O-alkyl-glyceryl-3-phosphorylcholine) (lyso-PAF-acether). Formation of the latter probably results from the activation of a phospholipase A2 (PLA2). Indeed, the PLA2 inhibitors, bromophenacyl bromide (BPB), mepacrine, 874CB (100 μM), and EDTA (5 mM), blocked the zymosan-induced release of PAF-acether from PC. EDTA and BPB also markedly reduced the release of lyso-PAF-acether. PAF-acether formation could involve a metabolic step linking the acetyl moiety to the 2nd carbon of lyso-PAF-acether. To verify this hypothesis, acetyl coenzyme A (acetyl-CoA) was added to stimulated PC. This enhanced the release of PAF-acether in a dose-dependent fashion from 1 μM acetyl-CoA to reach a maximal increase −200%—at 100 μM. Furthermore, using3H acetyl-CoA, incorporation of labelled acetate into PAF-acether was suggested by (1) identical chromatographic patterns of biological activity and radioactivity; (2) disappearance of these activities after treatment with PLA2, but not after exposure to lipase fromRhizopus arrhizus. PAF-acether was also obtained when both acetyl-CoA (100 μM) and synthetic lyso-PAF-acether (0.2 μM) were added to unstimulated PC previously treated with BPB (100 μM for 10 min). These results suggest that the release of PAF-acether is the consequence of at least two different steps: (1) hydrolysis of 1-O-alkyl-2-acyl-glyceryl-phosphorylcholine by PLA2; (2) enzymatic acetylation of the hydrolysis product.


Lipase Acetyl Hydrolysis Product Cell Source Mepacrine 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. [1]
    J. Benveniste, C.G. Cochrane andP.M. Henson,Leukocyte-dependent histamine release from rabbit platelets: The role of IgE, basophils and a platelet-activating factor, J. Exp. Med.136, 1356–1377 (1972).Google Scholar
  2. [2]
    J.M. Mencia-Huerta andJ. Benveniste,Platelet-activating factor (PAF) and macrophages. I. Evidence for the release from rat and mouse peritoneal macrophages and not from mastocytes, Eur. J. Immunol.9, 409–415 (1979).PubMedGoogle Scholar
  3. [3]
    J.M. Lynch, G.Z. Lotner, S.J. Betz andP.M. Henson,The release of platelet-activating factor by stimulated rabbit neutrophils, J. Immunol.123, 1219–1226 (1979).PubMedGoogle Scholar
  4. [4]
    M. Chignard, J.P. Le Couedic, M. Tence, B.B. Vargaftig andJ. Benveniste,The role of platelet-activating factor in platelet aggregation, Nature279, 799–800 (1979).PubMedGoogle Scholar
  5. [5]
    C.A. Demopoulos, R.N. Pinckard andD.J. Hanahan,Platelet-activating factor. Evidence for 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine as the effective component (a new class of lipid chemical mediators), J. Biol. Chem.254, 9355–9358 (1979).PubMedGoogle Scholar
  6. [6]
    J. Benveniste, M. Tence, P. Varenne, J. Bidault, C. Boullet andJ. Polonsky,Semi-synthèse et structure proposée du facteur activant les plaquettes (PAF): PAF-acéther, un alkyl éther analogue de la lysophosphatidylcholine, C.R. Acad. Sci. Paris289D, 1037–1040 (1979).Google Scholar
  7. [7]
    J.J. Godfroid, F. Heymans, E. Michel, C. Redeuilh, E. Steiner andJ. Benveniste,Platelet-activating factor (PAF-acether): Total synthesis of 1-O-octadecyl-2-O-acetyl-sn-glycero-3-phosphorylcholine. FEBS Lett.116, 161–164 (1980).CrossRefPubMedGoogle Scholar
  8. [8]
    J. Polonsky, M. Tence, P. Varenne, B.C. Das, J. Lunel andJ. Benveniste,Release of 1-O-alkyl-glyceryl-3-phosphorylcholine, O-deacetyl platelet-activating factor (lyso-PAF-acether) from leukocytes. Chemical ionization mass spectrometry of phospholipids, Proc. Natn. Acad. Sci. USA717, 1019–1028 (1980).Google Scholar
  9. [9]
    J.M. Mencia-Huerta, C. Akerman andJ. Benveniste,Phospholipase A2 (PLA2), lipo (LO), cyclo (CO) oxygenases, and release of platelet-activating factor (PAF) and slow-reacting substance (SRS) from rat macrophages, Fedn Proc.39, 691 (Abs.) (1980).Google Scholar
  10. [10]
    H. Chap, G. Mauco, M.F. Simon, J. Benveniste andL. Douste-Blazy,Biosynthetic labelling of platelet-activating factor (PAF-acether) from radioactive acetate by stimulated platelets, Nature289, 312–314 (1981).CrossRefPubMedGoogle Scholar
  11. [11]
    R.L. Wykle, B. Malone andF. Snyder,Enzymatic synthesis of 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine, a hypotensive and platelet-aggregating lipid, J. Biol. Chem.255, 10256–10260 (1980).PubMedGoogle Scholar
  12. [12]
    E. Ninio, J.M. Mencia-Huerta, F. Heymans andJ. Benveniste,Biosynthesis of platelet-activating factor (PAF-acether). I. Evidence for an acetyl transferase activity in murine macrophages, Biochim. Biophys. Acta, in press (1981).Google Scholar

Copyright information

© Birkhäuser Verlag 1981

Authors and Affiliations

  • Jean Michel Mencia-Huerta
    • 1
  • Ewa Ninio
    • 1
  • Régine Roubin
    • 1
  • Jacques Benveniste
    • 1
  1. 1.INSERM U 200ClamartFrance

Personalised recommendations