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Pharmacological Control of Phospholipase A2 Activity In Vitro and In Vivo

  • Lisa A. Marshall
  • Joseph Y. Chang
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 275)

Abstract

Phospholipase(s)A2 (PLA2) are a class of enzymes that catalyze the hydrolysis of membrane phospholipids to liberate free fatty acids from the sn-2 position resulting in the formation of free fatty acids, predominantly arachidonic acid, and lysophospholipid. Within the last 20 years their role in disease has gained increasing attention (1,2,3). Various physiological stimuli (antigen-antibody complexes, cytokines, angiotensin II, bradykinin, prolactin and thrombin) activate PLA2 when added to responsive cells. Indeed, high levels of PLA2 activity have been found in joint fluid of patients with rheumatoid arthritis, in serum of patients with endotoxin shock or pancreatitis, in psoriatic lesions or peritoneal lavage fluids of patients with bacterial peritonitis. In some cases, enhanced levels of PLA2 correlate with disease severity and have been proposed for use as a biochemical marker of disease activity (4,5).

Keywords

Platelet Activate Factor Snake Venom Aristolochic Acid PLA2 Activity Peritoneal Lavage Fluid 
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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References

  1. 1.
    E. A. Dennis, Phospholipase A2 Mechanism: Inhibition and Role in Arachidonic Acid Release, Drug Dev. Res. 10:205 (1987).CrossRefGoogle Scholar
  2. 2.
    P. Vadas and W. Pruzanski, Biology of Disease: Role of Secretory Phospholipases A2 in the Pathobiology of Disease, Lab. Invest., 55:391 (1986).PubMedGoogle Scholar
  3. 3.
    J. Chang, J. H. Musser and H. McGregor, Phospholipase A2: Function and Pharmacological Regulation, Biochem. Pharmacol. 36:2429 (1987).PubMedCrossRefGoogle Scholar
  4. 4.
    P. Vadas, Elevated Plasma Phospholipase A2 Levels: Correlation with the Hemodynamic and Pulmonary Changes in Gram-Negative Septic Shock, J. Lab. Clin. Med. 104:873 (1984).PubMedGoogle Scholar
  5. 5.
    S. Forster, E. Ilderton, J. F. B. Norris, R. Summerly and H. J. Yardley, Characterization and Activity of Phospholipase A2 in Normal Human Epidermis and in Lesion-Free Epidermis of Patients with Psoriasis or Eczema, Br. J. Dermatol. 112:135 (1985).PubMedCrossRefGoogle Scholar
  6. 6.
    S. C. Gilman, J. Chang, P. R. Zeigler, J. Uhl and E. Mochan, Interleukin-1 Activates Phospholipase A2 in Human Synovial Cells, Arthritis Rheum. 31:126(1988).PubMedCrossRefGoogle Scholar
  7. 7.
    W. Pruzanski, P. Vadas, J. Kim, H. Jacobs and E. Stefanski, Phospholipase A2 Activity Associated with Synovial Fluid Cells, J. Rheumatol. 15:791 (1988).PubMedGoogle Scholar
  8. 8.
    J. Chang, S. C. Gilman and A. J. Lewis, Interleukin-1 Activates Phospholipase A2 in Rabbit Chondrocytes: A possible Signal for IL-1 Action, J. Immunol. 136:1283(1986).PubMedGoogle Scholar
  9. 9.
    J. N. Hawthorne and M. R. Pickard, Phospholipids in Synaptic Function, J. Neurochem. 32:5 (1979).PubMedCrossRefGoogle Scholar
  10. 10.
    F. Snyder, M. L. Blank, D. Johnson, T. Lee, B. Malone, M. Robinson and D. S. Woodard, Alkylacetylglycerols Versus Lyso-PAF as Precursors in PAF Biosynthesis and the Role of Arachidonic Acid in PAF Metabolism, Pharmacol. Res. Commun., 18:33 (1986).PubMedCrossRefGoogle Scholar
  11. 11.
    A. Etienne, F. Hecquet, C. Soulard, C. Touvay, F. Clostre and P. Braquet, The Relative Role of PAF-Acether and Icosanoids in Septic Shock, Pharmacol. Res. Commun., 18:71 (1986).PubMedCrossRefGoogle Scholar
  12. 12.
    G. H. Higgs, B. Henderson, S. Moncada and J. A. Salmon, The Synthesis and Inhibition of Eicosanoids in Inflammation, in: “Inflammatory Mediators”, G. A. Higgs and T. J. Williams, eds., VCH, Great Britain (1985).Google Scholar
  13. 13.
    R. J. Flower, Lipocortin and the Mechanism of Action of the Glucocorticoids, Br. J. Pharmacol. 94:987 (1988).PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    D. Mobilio and L. A. Marshall, Recent Advances in the Design and Evaluation of Inhibitors of Phospholipase A2, in: “Annual Reports in Medicinal Chemistry”, Vol. 24, R. C. Allen, ed., Academic Press, Inc., New York (1989).Google Scholar
  15. 15.
    R. M. Kramer, C. Hession, B. Johansen, G. Hayes, P. McGray, E. P. Chow, R. Tizard, and R.B. Pepinsky, Structure and Properties of a Human Non-Pancreatic Phospholipase A2, J. Biol. Chem. 264(10):5768 (1989).PubMedGoogle Scholar
  16. 16.
    A. Pluckthun and E.A. Dennis, Activation, Aggregation, and Product Inhibition of Cobra Venom Phospholipase A2 and Comparison with Other Phospholipases, J. Biol. Chem. 260:11099 (1985).PubMedGoogle Scholar
  17. 17.
    P. Patriarca, S. Beckerdite, and P. Elsbach, Phospholipases and Phospholipid Turnover in Escherichia coli Spheroplasts, Biochim. Biophys. Acta 260:593(1972).PubMedCrossRefGoogle Scholar
  18. 18.
    K. B. Glaser and R. S. Jacobs, Inactivation of Bee Venom Phospholipase A2 by Manoalide, Biochem. Pharmaco. 36:2079 (1987).CrossRefGoogle Scholar
  19. 19.
    M. H. Gelb, Fluoro Ketone Phospholipid Analogues: New Inhibitors of Phospholipase A2, J. Am. Chem. Soc. 108:3146 (1986).CrossRefGoogle Scholar
  20. 20.
    C. F. Bennett, S. Mong, M. A. Clarke, L. I. Kruse, and S. T. Crooke, Differential Effects of Manoalide on Secreted and Intracellular Phospholipases, Biochem. Pharmacol. 36:733 (1987).PubMedCrossRefGoogle Scholar
  21. 21.
    B. S. Vishwanath, A. A. Fauzy, R. C. Franson, Edema-inducing Activity of Phospholipase A2 Purified From Human Synovial Fluid and Inhibition by Aristolochic Acid. Inflammation, 12:549(1988).PubMedCrossRefGoogle Scholar
  22. 22.
    J. L. Humes, S. Sadowski, M. Galavage, M. Goldenberg, E. Subers, R. J. Bonney, F.A. Kuehl, Jr., Evidence for Two Sources of Arachidonic Acid for Oxidative Metabolism by Mouse Peritoneal Macrophages, J. Biol. Chem. 257:1591 (1982).PubMedGoogle Scholar
  23. 23.
    A. M. S. Mayer, K. B. Glaser, and R. S. Jacobs, Regulation of Eicosanoid Biosynthesis In Vitro and In Vivo by the Marine Natural Product Manoalide: A Potent Inactivator of Venom Phospholipases, J. Pharmacol. Exp. Ther., 244:871 (1987).Google Scholar
  24. 24.
    M. Baggiolini, J. Schnyder, B. Dewald, U. Bretz, and T. G. Payne, Phagocytosis-Stimulated Macrophages, Production of Prostaglandins and SRS-A, and Prostaglandin Effects on Macrophage Activation, Immunobiol. 161:369 (1982).CrossRefGoogle Scholar
  25. 25.
    L. A. Marshall, Arachidonic Acid Metabolism of Cultured Peritoneal Rat Macrophages and its Manipulation by Nonsteroidal Antiinflammatory Agents, Immunopharmacol. 15:177 (1988).CrossRefGoogle Scholar
  26. 26.
    A. J. Lewis, R. P. Carlson, and J. Chang, Experimental Models of Inflammation, in: “Handbook of Inflammation” Vol. 5,I. L. Bonta, M. A. Bray, and M. J. Parnham, eds., Elsevier Science Publishers B.V., New York (1985)Google Scholar
  27. 27.
    L. A. Marshall, J.Y. Chang, W. Calhoun, J. Yu, and R. P. Carlson, Preliminary Studies on Phospholipase A2-induced Mouse Paw Edema as a Model to Evaluate Antiinflammatory Agents, J. Cell. Biochem. 40:147 (1989).PubMedCrossRefGoogle Scholar
  28. 28.
    G. Cirino, S. H. Peers, J. L. Wallace, and R. J. Flower, A Study of Phospholipase A2-induced Oedema in Rat Paw, Eur. J. Pharmacol. 166:505 (1989).PubMedCrossRefGoogle Scholar
  29. 29.
    M. R. Kerman and J. D. Faulkner, The Luffarrellins, Novel Antiinflammatory Sesteterpenes of Chemotaxononic Importance from the Marine Sponge Luffariella Vareabilis, J. Org. Chem. 52:3081 (1987).CrossRefGoogle Scholar
  30. 30.
    W. Calhoun, J. Yu, B. M. Weichman, T. T. Chau, L. A. Marshall, and R. P. Carlson, Pharmacologic Modulation of Phospholipase A2-induced Paw Edema in the Mouse, Agents Actions 27:418 (1989).PubMedCrossRefGoogle Scholar
  31. 31.
    J. W. Berkenkopf, L. A. Marshall, B. M. Weichman, Phospholipase A2-induced Inflammation in Rats, Tissue Reactions, in press.Google Scholar
  32. 32.
    J. W. Berkenkopf and B. M. Weichman, Differential Effects of Antiinflammatory Drugs on Fluid Accumulation and Cellular Infiltration in Reverse Passive Arthus Pleurisy and Carrageenan Pleurisy in Rats, Pharmacol. 34:309 (1987).CrossRefGoogle Scholar
  33. 33.
    B. M. Weichman, J. W. Berkenkopf, C. A. Cullinan, and R. J. Sturm, Leukotriene B4 Production and Pharmacologic Regulation of Reverse Passive Arthus Pleurisy: Importance of Antigen Dose, Agents Actions 21:351 (1987).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Lisa A. Marshall
    • 1
  • Joseph Y. Chang
    • 1
  1. 1.Wyeth-Ayerst ResearchPrincetonUSA

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