Activation of 85 kDa PLA2 by Eicosanoids in Human Neutrophils and Eosinophils

  • Robert L. Wykle
  • Jonny Wijkander
  • Andrew B. Nixon
  • Larry W. Daniel
  • Joseph T. O’Flaherty
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 416)


The initial step in the remodeling pathway of PAF synthesis is catalyzed by phospholipase A2 (PLA2).1 It has generally been accepted that PLA2 acts directly on 1-0-alkyl-2-arachidonoyl-sn-glycero-3-phosphocholine (alkyl-2-AA-GPC) to form lyso-PAF (1-alkyl-2-lyso-GPC) which is then acetylated to yield PAF. More recent studies suggest that PAF synthesis may also be initiated indirectly through the action of CoA-independent transacylase following the hydrolysis of l-0-alk-1′-enyl-2-AA-sn-glycero-3-phosphoethanolamine (alkenyl-2-AA-GPE) by PLA2.2,3 In the putative indirect pathway, an accumulation of alkenyl-2-lyso-GPE triggers the transfer of AA from alkyl-2-AA-GPC to the alkenyl-2-lyso-GPE thus forming lyso-PAF. It seems logical that both the direct and indirect pathways may contribute to PAF synthesis. However, the relative physiological importance of the two pathways has not been established.


Human Neutrophil Arachidonic Acid Release Lipoxygenase Product Free Arachidonic Acid Pancreatic PLA2 
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.
    Prescott, S. M., Zimmerman, G. A., and McIntyre, T. M.: Platelet-activating factor. J. Biol. Chem. 265: 17381–17384 (1990).PubMedGoogle Scholar
  2. 2.
    Nieto, M. L., Venable, M. E., Bauldry, S. A., Greene, D. G., Kennedy, M., Bass, D. A., and Wykle, R. L.: Evidence that hydrolysis of ethanolamine plasmalogens triggers synthesis of platelet activating factor via a transacylation reaction. J. Biol. Chem. 266: 18699–18706 (1991).PubMedGoogle Scholar
  3. 3.
    Uemura, Y., Lee, T.-C., and Snyder, F.: A coenzyme A-independent transacylase is linked to the formation of platelet-activating factor (PAF) by generating the lyso-PAF intermediate in the remodeling pathway. J. Biol. Chem. 266: 8268–8272 (1991).PubMedGoogle Scholar
  4. 4.
    Ramesha, C. S., and Pickett, W. C.: Platelet-activating factor and leukotriene biosynthesis is inhibited in polymorphonuclear leukocytes depleted of arachidonic acid. J. Biol. Chem. 261: 7592–7595 (1986).PubMedGoogle Scholar
  5. 5.
    Suga, K., Kawasaki, T., Blank, M. L., and Snyder, F.: An arachidonoyl (polyenoic)-specific phospholipase A, activity regulates the synthesis of platelet-activating factor in granulocytic HL-60 cells. J. Biol. Chem. 265: 12363–12371 (1990).Google Scholar
  6. 6.
    Billah, M. M., Bryant, R. W., and Siegel, M. I.: Lipoxygenase products of arachidonic acid modulate biosynthesis of platelet-activating factor (1–0-alkyl-2-acetyl-sn-glycerol-3-phosphocholine) by human neutrophils via phospholipase A,. J. Biol. Chem. 260: 6899–6906 (1985).PubMedGoogle Scholar
  7. 7.
    Tessner, T. G., O’Flaherty, J. T., and Wykle, R. L.: Stimulation of platelet-activating factor synthesis by a nonmetabolizable bioactive analog of platelet-activating factor and influence of arachidonic acid metabolites. J. Biol. Chem. 264: 4794–4799 (1989).PubMedGoogle Scholar
  8. 8.
    Chilton, F. H., O’Flaherty, J. T., Ellis, J. M., Swendsen, C. L., and Wykle, R. L.: Selective acylation of lyso platelet activating factor by arachidonate in human neutrophils. J. Biol. Chem. 258: 7268–7271 (1983).PubMedGoogle Scholar
  9. 9.
    Mueller, H. W., O’Flaherty, J. T., Greene, D. G., Samuel, M. P., Wykle, R. L.: 1–0-alkyl-linked glycerophospholipids of human neutrophils: Distribution of arachidonate and other acyl residues in the ether-linked and diacyl species. J. Lipid Res. 25: 383–388 (1984).PubMedGoogle Scholar
  10. 10.
    Ramesha, C. S. and Ives, D. L.: Detection of arachidonoyl-selective phospholipase A, in human neutrophil cytòsol. Biochim. Biophys. Acta. 1168: 37–44 (1993).PubMedCrossRefGoogle Scholar
  11. 11.
    Alonso, F., Henson, R. M., and Leslie, C. C.: A cytosolic phospholipase in human neutrophils that hydrolyzes arachidonoyl-containing phosphatidylcholine. Biochim. Biophys. Acta. 878: 273–280 (1986).PubMedCrossRefGoogle Scholar
  12. 12.
    Lin, L.-L., Lin, A. Y., and Knopf, J. L.: Cytosolic phospholipase A, is coupled to hormonally regulated release of arachidonic acid. Proc. Natl. Acad. Sci. 89: 6147–6151 (1992).PubMedCrossRefGoogle Scholar
  13. 13.
    Wijkander, J., O’Flaherty, J. T., and Wykle, R. L.: 5-Lipoxygenase products modulate the activity of the 85 kDa phospholipase A, in human neutrophils. J. Biol. Chem., in press.Google Scholar
  14. 14.
    Powell, W. S., Gravel, S., MacLeod, R. J., Mills, E., and Hashefi, M.: Stimulation of human neutrophils by 5-oxo-6,8,11,14-eicosatetraenoic acid by a mechanism independent of the leukotriene B4 receptor. J. Biol. Chem. 268: 9280–9286 (1993).PubMedGoogle Scholar
  15. 15.
    Bauldry, S. A., Wykle, R. L., and Bass, D. A.: Phospholipase A, activation in human neutrophils. Differential actions of diacylglycerols and alkylacylglycerols in priming cells for stimulation by N-formyl-met-leuphe. J. Biol. Chem. 263: 16787–16795 (1988).PubMedGoogle Scholar
  16. 16.
    Bauldry, S. A., Wykle, R. L., and Bass, D. A.: Differential actions of diacyl-and alkylacylglycerols in priming phospholipase A„ 5-lipoxygenase and acetyltransferase activation in human neutrophils. Biochim. Biophys. Acta 1084: 178–184 (1991)PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Robert L. Wykle
    • 1
  • Jonny Wijkander
    • 1
  • Andrew B. Nixon
    • 1
  • Larry W. Daniel
    • 1
  • Joseph T. O’Flaherty
    • 1
  1. 1.Department of BiochemistryBowman Gray School of MedicineWinston-SalemUSA

Personalised recommendations