Advertisement

Phospholipase A2 Activation is the Pivotal Step in the Effector Pathway of Inflammation

  • Peter Vadas
  • Waldemar Pruzanski
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 275)

Abstract

Our understanding of the mechanisms of initiation and propagation of local and systemic inflammatory processes is clearly imperfect if one uses the available therapeutic modalities as a yardstick. While glucocorticoids are potent anti-inflammatory drugs, the pharmacologic target of this class of agents has not been identified with certainty, and the use of steroids is fraught with the risk of considerable and potentially dangerous side effects. On the other hand, non-steroidal anti-inflammatory drugs (NSAIDS), while more specific, are relatively weak anti-inflammatory compounds and frequently require the addition of more potent agents. Cytotoxic drugs or anti-metabolites effectively suppress acute and chronic inflammatory reactions, but also predispose to infection and initiate the development of neoplasms following long-term exposure.The inadequacy and relative non-specificity of these approaches underscore the deficiencies in our understanding of the principles that govern these responses. A better understanding of these processes will be applicable to broad categories of human disease including autoimmunity, the collagen vascular diseases, aberrations in host defense and the response to trauma and infection.

Keywords

Septic Shock Acute Lung Injury Platelet Activate Factor Aristolochic Acid Effector Pathway 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    W. B. Coley, The treatment of malignant tumours by repeated innoculations of erysipelas: With a report of ten original cases. Am. J. Med. Sci. 105:487 (1893).CrossRefGoogle Scholar
  2. 2.
    M. J. Shear, Chemical treatment of tumours. IX. Reactions of mice with primary subcutaneous tumours to injection of hemorrhage-producing bacterial polysaccharide. J. Natl. Canc. Inst. 5:185 (1944).Google Scholar
  3. 3.
    E. A. Carswell, L. J. Old, R. L. Kassel, et al. An endotoxin-induced serum factor that causes necrosis of tumours. Proc. Natl. Acad. Sci. USA 72:3666 (1975).PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    M. Kawakami, P. H. Pekala, M. D. Lane, et al. Lipoprotein lipase suppression in 3T3-L1 cells by an endotoxin-induced mediator from exudate cells. Proc. Natl. Acad. Sci. USA 79:912 (1982).PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    B. Beutler, J. Mahoney, N. Le Trang, et al. Purification of cachectin, a lipoprotein lipase-suppressing hormone secreted by endotoxin-induced RAW 264.7 cells. J. Exp. Med. 161:984 (1985).PubMedCrossRefGoogle Scholar
  6. 6.
    M. G. Rosenblum and N. J. Donato. Tumour necrosis factor alpha: A multifaceted peptide hormone. Crit. Rev. Immunol. 9:21 (1989).PubMedGoogle Scholar
  7. 7.
    G. E. Nedwin, S. L. Naylor, A. Y. Sakaguchi, et al. Human lymphotoxin and tumour necrosis factor genes: structure homology and chromosomal localization. Nucleic Acids Res. 13:6361 (1985).PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    M. A. Palladino Jr., M. R. Shalaby, S. M. Kramer et al. Characterization of the antitumour activities of human tumour necrosis factor alpha and the comparison with the other cytokines: induction of tumour-specific immunity. J. Immunol. 138:4023 (1987).PubMedGoogle Scholar
  9. 9.
    B. Beutler. Orchestration of septic shock by cytokines: The role of cachectin (tumour necrosis factor), in: “Molecular and Cellular Mechanisms of Septic Shock”, Alan R. Liss, New York (1989).Google Scholar
  10. 10.
    B. Beutler, N. Krochin, I. W. Milsark, et al. Control of cachectin (tumour necrosis factor) synthesis: mechanisms of endotoxin resistance. Science 232:977 (1986).PubMedCrossRefGoogle Scholar
  11. 11.
    D. G. Remick, R. M. Strieter, J. P. Lynch, et al. In vivo dynamics of murine tumour necrosis factor alpha gene expression. Kinetics of dexamethasone-induced suppression. Lab. Invest. 60:766 (1989).PubMedGoogle Scholar
  12. 12.
    S. S. Boggs, D. R. Boggs, and R. A. Joyce. Response to endotoxin of endotoxin-resistant C3H/HeJ mice: a model for study of hematopoietic control. Blood 55:444 (1980).PubMedGoogle Scholar
  13. 13.
    K. J. Tracey, S. F. Lowry, and A. Cerami. Cachectin: a hormone that triggers acute shock and chronic cachexia. J. Infect. Dis. 157:413 (1988).PubMedCrossRefGoogle Scholar
  14. 14.
    S. Q. Simpson and L. C. Casey. Role of tumour necrosis factor in sepsis and acute lung injury. Critical Care Clinics 5:27 (1989).PubMedGoogle Scholar
  15. 15.
    M. Blick, S. A. Shervin, M. Rosenblum, and J. Gutterman. Phase 1 study of recombinant tumour necrosis factor in cancer patients. Cancer Res. 47:2986 (1987).PubMedGoogle Scholar
  16. 16.
    A. F. Suffredini, R. F. Fromm, M. M. Parker, et al. The cardiovascular response of normal humans to the administration of endotoxin. N. Engl. J. Med. 321:280 (1989).PubMedCrossRefGoogle Scholar
  17. 17.
    H. R. Michie, K. R. Manogue, D. R. Spriggs, et al. Detection of circulating tumour necrosis factor after endotoxin administration. N. Engl. J. Med. 318:1481 (1988).PubMedCrossRefGoogle Scholar
  18. 18.
    B. A. Beutler, I. W. Milsark, and A. Cerami. Cachectin/tumour necrosis factor: production, distribution, and metabolic fate in vivo. J. Immunol. 135:3972 (1985).PubMedGoogle Scholar
  19. 19.
    B. Beutler, I. W. Milsark, and A. Cerami. Passive immunization against cachectin/tumour necrosis factor (TNF) protects mice from the lethal effect of endotoxin. Science 229:869 (1985).PubMedCrossRefGoogle Scholar
  20. 20.
    K. J. Tracey, Y. Fong, D. G. Hesse, et al. Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteremia. Nature 330:662 (1987).PubMedCrossRefGoogle Scholar
  21. 21.
    C. A. Dinarello, and N. Savage. Interleukin-1 and its receptor. Critical Rev. Immunol. 9:1 (1989).Google Scholar
  22. 22.
    S. Demczuk, D. Baumberger, B. Mach, and J.-M. Dayer. Expression of human IL-1 alpha and beta messenger RNAs and IL-1 activity in human peripheral blood mononuclear cells. J. Mol. Cell. Immunol. 3:225 (1987).Google Scholar
  23. 23.
    B. Lepe-Zuniga, and I. Gery. Production of intracellular and extracellular interleukin-1 (IL-1) by human monocytes. Clin. Immunol. Immunopathol. 31:222 (1984).PubMedCrossRefGoogle Scholar
  24. 24.
    G. W. Duff and E. Atkins. The detection of endotoxin by in vitro production of endogenous pyrogen: Comparison with limulus amebocyte lysate gelation. J. Immunol. Methods. 52:323 (1982).PubMedCrossRefGoogle Scholar
  25. 25.
    A. Waage, P. Brandtzaeg, A. Halstensen, P. Kierulf, and T. Espevik. The complex pattern of cytokines in serum from patients with meningococcal septic shock. J. Exp. Med. 169:333 (1989).PubMedCrossRefGoogle Scholar
  26. 26.
    S. Okusawa, J. A. Gelfand, T. Ikejima, R. J. Connolly, and C. A. Dinarello. Interleukin 1 induces a shock-like state in rabbits. Synergism with tumour necrosis factor and the effect of cyclooxygenase inhibition. J. Clin. Invest. 81:1162 (1988).PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    C. A. Dinarello, J. G. Cannon, S. M. Wolff, et al. Tumour necrosis factor (cachectin) is an endogenous pyrogen and induces production of interleukin 1. J. Exp. Med. 163:1433 (1986).PubMedCrossRefGoogle Scholar
  28. 28.
    P. J. Knudsen, C. A. Dinarello, and T. B. Strom. Glucocorticoids inhibit transcriptional and post-transcriptional expression of interleukin 1 in U937 cells. J. Immunol. 139:4129 (1987).PubMedGoogle Scholar
  29. 29.
    J. R. Weinberg, D. J. M. Wright, and A. Guz. Interleukin-1 and tumour necrosis factor cause hypotension in the conscious rabbit. Clin. Science 75:251 (1988).Google Scholar
  30. 30.
    C. A. Dinarello. Interleukin-1. Rev. Infect. Dis. 6:51 (1984).PubMedCrossRefGoogle Scholar
  31. 31.
    S. E. Goldblum, D. A. Cohen, M. N. Gillespie and C. J. McClain. Interleukin-1-induced granulocytopenia and pulmonary leukostasis in rabbits. J. Appl. Physiol. (in press).Google Scholar
  32. 32.
    C. A. Dinarello, S. Okusawa, and J. A. Gelfand. Interleukin-1 induces a shock-like state in rabbits: synergism with tumour necrosis factor and the effect of cyclooxygenase inhibition, in: Molecular and Cellular Mechanisms of Septic Shock. Alan R. Liss, New York (1989).Google Scholar
  33. 33.
    B. Everaerdt, P. Brouckaert, A. Shaw, and W. Fiers. Four different interleukin-1 species sensitize to the lethal action of tumour necrosis factor. Biochem. Biophys. Res. Comm. 163:378 (1989).PubMedCrossRefGoogle Scholar
  34. 34.
    R. M. Kramer, J. A. Jakubowski, and D. Deykin. Hydrolysis of l-alkyl-2-arachidonoyl-sn-glycero-3-phosphocholine, a common precursor of platelet-activating factor and eicosanoids, by human platelet phospholipase A2. Biochim. Biophys. Acta 959:269 (1988).PubMedCrossRefGoogle Scholar
  35. 35.
    F. H. Chilton, M. J. Ellis, S. C. Olson, and R. L. Wykle. l-O-alkyl-2-arachidonyl-sn-glycero-3-phosphocholine: a common source of platelet activating factor and arachidonate in human polymorphonuclear leukocytes. J. Biol. Chem. 259:12014 (1984).PubMedGoogle Scholar
  36. 36.
    T. Ch. Lee, B. Malone, and F. Snyder. A new de novo pathway for the formation of l-alkyl-2-acetyl-sn-glycerols, precursors of platelet activating factor. Biochemical characterization of l-alkyl-2-lyso-sn-glycero-3-P: acetyl-CoA acetytransferase in rat spleen. J. Biol. Chem. 261:5373 (1986).PubMedGoogle Scholar
  37. 37.
    P. Braquet and M. Rola-Pleszcynski. Platelet-activating factor and cellular immune responses. Immunol. Today 8:345 (1987).CrossRefGoogle Scholar
  38. 38.
    Y. Thomas, Y. Denizot, E. Dassa, C. Boullet, and J. Benveniste. Synthese du paf-acether par E. coli K12. C. R. Acad. Sci. Paris 303:699 (1986).PubMedGoogle Scholar
  39. 39.
    P. Braquet, M. Paubert-Braquet, P. Bessin, and B. B. Vargaftig. Platelet-activating factor: a potential mediator of shock. Adv. Prostaglandin Thromboxane Leukotriene Res. 17:822 (1987).Google Scholar
  40. 40.
    X.-M. Sun and W. Hsueh. Bowel necrosis induced by tumour necrosis factor in rats is mediated by platelet-activating factor. J. Clin. Invest. 81:1328 (1988).PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    K.-M. Chu, J. G. Gerber and A. S. Nies. Local vasodilator effect of platelet activating factor in the gastric, mesenteric and femoral arteries of the dog. J. Pharmacol. Exp. Ther. 246:996 (1988).PubMedGoogle Scholar
  42. 42.
    V. Lagente, Z. B. Fortes, J. Garcia-Leme, and B. B. Vargaftig. PAF-acether and endotoxin display similar effects on rat mesenteric microvessels: inhibition by specific antagonists. J. Pharmacol. Exp. Ther. 247:254 (1988).PubMedGoogle Scholar
  43. 43.
    G. Feuerstein, and A. L. Siren. Platelet-activating factor and shock. Prog. Biochem. Pharmacol. 22:181 (1988).PubMedGoogle Scholar
  44. 44.
    C. Kroegel. The potential pathophysiological role of platelet-activating factor in human diseases. Klin. Wochenschr. 66:373 (1988).PubMedCrossRefGoogle Scholar
  45. 45.
    A. M. Lefer. Eicosanoids as mediators of ischemia and shock. Federation Proc. 44:275 (1985).Google Scholar
  46. 46.
    A. M. Lefer. Leukotrienes as mediators of ischemia and shock. Biochem. Pharmacol. 35:123 (1986).PubMedCrossRefGoogle Scholar
  47. 47.
    W. Oettinger, B. A. Peskar, and H. G. Beger. Profiles of endogenous prostaglandins F2a, thromboxane A2 and prostacyclin with regard to cardiovascular and organ functions in early septic shock in man. Eur. Surg. Res. 19:65 (1987).PubMedCrossRefGoogle Scholar
  48. 48.
    M. E. Doerfler, R. L. Danner, J. H. Shelhamer, and J. E. Parrillo. Bacterial lipopolysaccharides prime human neutrophils for enhanced production of leukotriene B4. J. Clin. Invest. 83:970 (1989).PubMedCentralPubMedCrossRefGoogle Scholar
  49. 49.
    G. Feuerstein, and J. M. Hallenbeck. Prostaglandins, leukotrienes, and platelet-activating factor in shock. Annu. Rev. Pharmacol. Toxicol. 27:301 (1987).PubMedCrossRefGoogle Scholar
  50. 50.
    T. Schonhardt and E. Ferber. Translocation of phospholipase A2 from cytosol to membranes induced by l-oleoyl-2-acetyl-glycerol in serum-free cultured macrophages. Biochem. Biophys. Res. Comm. 149:769 (1987).PubMedCrossRefGoogle Scholar
  51. 51.
    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
  52. 52.
    J. Seilhamer, P. Vadas, W. Pruzanski, S. Plant, E. Stefanski and L. Johnson. Synovial fluid phospholipase A2 in arthritis. in: “Therapeutic approaches to inflammatory diseases”. A. J. Lewis, N. S. Doherty, and N. R. Ackerman, eds., Elsevier, New York (1989).Google Scholar
  53. 53.
    J. J. Seilhamer, W. Pruzanski, P. Vadas, S. Plant, J. A. Miller, J. Kloss, and L. K. Johnson. Cloning and recombinant expression of phospholipase A2 present in rheumatoid arthritic synovial fluid. J. Biol. Chem. 264:5335 (1989).PubMedGoogle Scholar
  54. 54.
    J. J. Seilhamer, S. Plant, W. Pruzanski, J. Schilling, E. Stefanski, P. Vadas, and L. K. Johnson. Multiple forms of phospholipase A2 in arthritic synovial fluid. J. Biochem. 106:38 (1989).PubMedGoogle Scholar
  55. 55.
    R. M. Kramer, C. Hession, B. Johansen, et al. Structure and properties of a human non-pancreatic phospholipase A2. J. Biol. Chem. 264:5768 (1989).PubMedGoogle Scholar
  56. 56.
    C.-Y. Lai and K. Wada. Phospholipase A2 from human synovial fluid: purification and structural homology to the placental enzyme. Biochem. Biophys. Res. Comm. 157:488 (1988).PubMedCrossRefGoogle Scholar
  57. 57.
    P. Vadas, W. Pruzanski, E. Stefanski, et al. Extracellular phospholipase A2 secretion is a common effector pathway of interleukin-1 and tumour necrosis factor action. (submitted for publication).Google Scholar
  58. 58.
    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
  59. 59.
    S. C. Gilman, J. Chang, P. R. Zeigler, J. Uhl, and E. Mochan. Interleukin-1 activates phospholipase A2 in human synovial cells. Arthritis Rheumatism 31:126 (1988).PubMedCrossRefGoogle Scholar
  60. 60.
    J. Pfeilschifter, W. Pignat, K. Vosbeck, and F. Marki. Interleukin 1 and tumour necrosis factor synergistically stimulate prostaglandin synthesis and phospholipase A2 release from rat renal mesangial cells. Biochem. Biophys. Res. Comm. 159:385 (1989).PubMedCrossRefGoogle Scholar
  61. 61.
    C. Lanni and E. Becker. Release of phospholipase A2 from rabbit peritoneal neutrophils by f-Met-Leu-Phe. Am. J. Pathol. 113:90 (1983).PubMedCentralPubMedGoogle Scholar
  62. 62.
    P. Vadas and J. B. Hay. The release of phospholipase A2 from aggregated platelets and stimulated macrophages of sheep. Life Sci. 26:1721 (1980).PubMedCrossRefGoogle Scholar
  63. 63.
    P. Vadas, W. Pruzanski, E. Stefanski, et al. Pathogenesis of hypotension in septic shock: correlation of circulating phospholipase A.2. levels with circulatory collapse. Critical Care Med. 16:1 (1988).CrossRefGoogle Scholar
  64. 64.
    P. Vadas and J. B. Hay. The appearance and significance of phospholipase A2 in lymph draining tuberculin reactions. Am. J. Pathol. 107:285 (1982).PubMedCentralPubMedGoogle Scholar
  65. 65.
    J. R. Traynor and K. S. Authi. Phospholipase A2 activity of lysosomal origin secreted by polymorphonuclear leukocytes during phagocytosis or on treatment with calcium. Biochim. Biophys. Acta 665:571 (1981).PubMedCrossRefGoogle Scholar
  66. 66.
    P. Vadas and J. B. Hay. Involvement of circulating phospholipase A2 in the pathogenesis of the hemodynamic changes in endotoxin shock in rabbits. Can. J. Physiol. Pharmacol. 61:561 (1983).PubMedCrossRefGoogle Scholar
  67. 67.
    P. Vadas, S. Wasi, H. Z. Movat and J. B. Hay. Extracellular phospholipase A2 mediates inflammatory hyperemia. Nature 273:583 (1981).CrossRefGoogle Scholar
  68. 68.
    H.-C. Huang. Release of slow reacting substance from the guinea-pig lung by phospholipases A2 of Vipera Russelli snake venom. Toxicon 22:359 (1984).PubMedCrossRefGoogle Scholar
  69. 69.
    J. Shaw, M. Roberts, R. Ulevitch, P. Henson, and E. Dennis. Phospholipase A2 contamination of cobra venom factor preparations. Am. J. Pathol. 91:571 (1978).Google Scholar
  70. 70.
    J. Edelson, W. Pruzanski, E. Stefanski and P. Vadas. Type I venom phospholipase A2 induces acute lung injury resembling ARDS. (submitted for publication).Google Scholar
  71. 71.
    P. Vadas, W. Pruzanski, J. Kim and V. Fornasier. The proinflammatory effect of intra-articular injection of soluble human and venom phospholipase A2. Am. J. Pathol. 134:807 (1989).PubMedCentralPubMedGoogle Scholar
  72. 72.
    B. S. Vishwanath, A. A. Fawzy, and 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
  73. 73.
    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
  74. 74.
    G. Cirino, S. H. Peers, J. L. Wallace, and R. J. Flower. A study of phospholipase A2-induced paw edema. Eur. J. Pharmacol. 166:505 (1989).PubMedCrossRefGoogle Scholar
  75. 75.
    G. E. Hoffmann, R. Hiefinger, and B. Steinbrueckner. Serum phospholipase A in hospitalized patients. Clin. Chim. Acta 183:59 (1989).PubMedCrossRefGoogle Scholar
  76. 76.
    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
  77. 77.
    G. Offenstadt, P. Pinta, J. Masliah, et al. Phospholipasic and prophospholipasic activities in bronchoalveolar lavage fluid in severe acute pulmonary disease with or without ARDS. Intensive Care Med. 7:285 (1981).PubMedCrossRefGoogle Scholar
  78. 78.
    P. Vadas, E. Stefanski and W. Pruzanski. Influence of plasma proteins on activity of pro-inflammatory enzyme phospholipase A2. Inflammation. 10:183 (1986).PubMedCrossRefGoogle Scholar
  79. 79.
    K. M. Conricode and R. S. Ochs. Mechanism for the inhibitory and stimulatory actions of proteins on the activity of phospholipase A2. Biochim. Biophys. Acta. 1003:36 (1989).PubMedCrossRefGoogle Scholar
  80. 80.
    P. Vadas, W. Pruzanski, E. Stefanski, et al. Concordance of endogenous Cortisol and phospholipase A2 levels in gram-negative septic shock. A prospective study. J. Lab. Clin. Med. 111:584 (1988).PubMedGoogle Scholar
  81. 81.
    W. Pruzanski, V. Farewell, and P. Vadas. Kinetics of phospholipase A2 clearance during convalescence from septic shock. (manuscript in preparation).Google Scholar
  82. 82.
    S. C. Gilman. Activation of rabbit articular chondrocytes by recombinant human cytokines. J. Rheumatol. 14:1002 (1987).PubMedGoogle Scholar
  83. 83.
    W. Pruzanski and P. Vadas. Studies on proinflammatory phospholipase A2, and the cytokine effector network. in: Biochemistry, molecular biology and physiology of phospholipase A2 and its regulatory factors. A. B. Mukherjee ed., Plenum Press, New York (in press).Google Scholar
  84. 84.
    W. Pruzanski, D. Wilmore, E. Stefanski and P. Vadas. Endotoxin-induced intravascular secretion of phospholipase A2 in healthy human volunteers: Relationship to tumour necrosis factor. (manuscript in preparation).Google Scholar
  85. 85.
    E. Ziegler, J. McCutchan, J. Fierer, et al. Treatment of gram-negative bacteremia and shock with human antiserum to a mutant E. coli. N. Engl. J. Med. 307:1226 (1982).Google Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Peter Vadas
    • 1
  • Waldemar Pruzanski
    • 1
  1. 1.Immunology Diagnostic and Research Centre Department of MedicineWellesley Hospital University of TorontoTorontoCanada

Personalised recommendations