Phospholipase A2 as Leukotriene B4 Secretagogue for Human Polymorphonuclear Leukocytes

  • Bing K. Lam
  • Chin-Yuh Yang
  • Patrick Y-K Wong
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 275)


High levels of soluble phospholipase A2 (PLA2) activity have been detected in tissues fluids associated with inflammatory diseases. However, the cellular origin for PLA2 has not been demonstrated. Several groups of investigators have proposed that platelets, macrophages and chondrocytes may be the cellular source of this enzyme. In fact, soluble PLA2 is secreted extracellularly from rabbit and rat chondrocytes and from human synovial cells in response to cytokine stimulation (1). PLA2 activity has been shown to be increased upon stimulation by the chemotactic peptide (f-met-leu-phe) and thrombin in neutrophils and platlets (2). PLA2 has been found to have pro-inflammatory effects and causes a dose dependent infiltration of leukocytes and increased vascular permeability (3). The vascular actions of PLA2 have been proposed to be mediated through the release of prostaglandin E2 and thromboxane (4). We have reported that purified PLA2 from snake venom stimulated the release of leukotrienes and lipoxins from endogenous sources in porcine leukocytes. However, there is no information regarding the mechanism of action of human PLA2 on inflammatory cells and the generation of leukotrienes. In this report, we present evidence that PLA2 isolated from human platelets can stimulate the production of leukotriene B4 from human polymorphonuclear leukocytes. These results suggest that soluble PLA2 may function as a secretagogue of LTB4 in inflammatory sites and further amplify the inflammatory processes by inducing chemotaxis of circulating leukocytes.


Arachidonic Acid Synovial Fluid Human Platelet Snake Venom Human Polymorphonuclear Leukocyte 
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  1. 1.
    Chang, J., Gilman, S.C. and Lewis, A.J.Interleukin-1 activates phospholipase A2 in rabbit chondrocytes: A possible signal for IL-1 action, J. Immunol. 136:1283, (1986).PubMedGoogle Scholar
  2. 2.
    Vadas, P., Pruzanski, W., Stefanski, E., Ellies, L., Aubin, J. Interleukin-1 induced syntehsis and secretion of extracellular phospholipase A2 from the cultured bone forming cells, International Conference on “Lipoproteins and Phospholipases”, Paris, France, September, (1988).Google Scholar
  3. 3.
    Purzanski, W. Experimental evidence for a proinflammatory effect of phospholipase A2 on joint tissue. J. Rheumat. 13, (1990), 1986.Google Scholar
  4. 4.
    Huang, H.C. Effects of phospholipases A2 from vipera russelli snake venom on blood pressure, plasma prostacyclin level and renin activity in rats, Toxicon, 22:253, (1984).PubMedCrossRefGoogle Scholar
  5. 5.
    Seilhamer, J.J., Pruzanski, W., Vadas, P., Plant, S., Miller, J.A., Kloss, J., Johnson, L.K. Cloning and recombinant expression of phospholipase A2 present in rheumatoid arthritic synovial fluid, J. Biol. Chem. 264: 5355, (1989).Google Scholar
  6. 6.
    Vadas, P., Pruzanski, W., Stefanski, E., Ellies, L., Aubin, J., IL-1 induces the synthesis and secretion of a soluble phospholipase A2 from fetal rat calvarial bone cells, Sclavo International Conference, (1989).Google Scholar
  7. 7.
    Seilhamer, J., Vadas, P., Purzanski, W., Plant, S., Stefanski, E. and Johnson, L. Synovial fluid phospholipase A2 in arthritis, in Therap. Approaches to inflammatory diseases. Ed. by J. Lewis, N.S. Doherty and N.R. Ackerman. Elsevier Science Press, Inc., NY, pp. 129, 1989.Google Scholar
  8. 8.
    Kramer, R.M., Hession, C., Johansen, B., Hayes, G., McGray, P., E.P. Tizard, R., Pepinsky, R.B. Structure and properties of a human non-pancreatic phospholipase A2 . J. Biol. Chem. 264, 5768, (1989).PubMedGoogle Scholar
  9. 9.
    Wong, P.Y-K, Lee, W., Chao, P.H-W, Reiss, R.F. and McGiff, J.C. Metabolism of prostacyclin by 9-hydroxyprostaglandin dehydrogenase in human platelets. J. Biol. Chem. 255:9021, (1980).PubMedGoogle Scholar
  10. 10.
    Parks, T.P. and Wong, P.Y-K. Purification of expoxygenase/ phospholipase A2 in human platelets, manuscript in preparation, (1990).Google Scholar
  11. 11.
    Wong, P.Y-K, Westlund, P., Hamberg, M., Granstrom, E., Chao, P.H-W and Samuelsson, B. ω-Hydroxylation of 12-HETE in human polymorphonuclear leukocytes. J. Biol. Chem. 259: 2683, (1984).PubMedGoogle Scholar
  12. 12.
    Borgeat, P. and Samuelsson, B. Arachidonic acid metabolism in polymorphonuclear leukocytes; effects of ionophore A23187, Proc. Natl. Acad. Sci. USA 76:2148, (1979).PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Powell, W.S. and Gravelle, F. Metabolism of leukotriene B4 to dihydro- and dihydro-oxo-products by procine leukocytes. J. Biol. Chem. 264: 5364, (1989).PubMedGoogle Scholar
  14. 14.
    Samuelsson, B., Leukotrienes.Mediators of immediate hypersensitivity reactions and inflammation, Sciences 220:568, 1983.CrossRefGoogle Scholar
  15. 15.
    Lam, B.K., Serhan, C.N., Samuelsson, B. and Wong, P.Y-K. A phospholipase A2 isoenzyme provokes lipoxin B formation from endogenous sources of arachidonic acid in porcine. Leukocytes. Biochem. Biophys. Res. Commun., 144: 123, 1987.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Bing K. Lam
    • 1
    • 3
  • Chin-Yuh Yang
    • 1
    • 2
  • Patrick Y-K Wong
    • 1
  1. 1.Departments of PhysiologyMedicine New York Medical CollegeValhallaUSA
  2. 2.Department of DentistryTri-Service General Hospital TaipeiTaiwanR.O.C.
  3. 3.Department of Rheumatol. and Immunol. Brigham and Women’s HospitalHarvard Medical SchoolBostonUSA

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