Skip to main content
SpringerLink
Log in

Circulating phospholipase A2 activity associated with sepsis and septic shock is indistinguishable from that associated with rheumatoid arthritis

  • Original Articles
  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

Elevation of circulating phospholipase A2 (PLA2) activity is associated with sepsis and septic shock. Elevated levels of PLA2 activity also are seen in association with chronic inflammatory disorders such as rheumatoid arthritis. The relationship between these phospholipases is unclear. We have developed a highly specific enzyme-linked immunosorbent assay (ELISA) capable of measuring human synovial PLA2 in plasma, using monoclonal antibodies raised to recombinant synovial PLA2. This ELISA has been used to quantitate circulating PLA2 levels in patients clinically diagnosed with sepsis. These elevated levels positively correlated with the elevation seen in plasma PLA2 enzyme activity. The antibodies also have been used to purify immunoreactive PLA2 from plasma of patients with sepsis, thus enabling characterization of the purified protein by amino-terminal sequence analysis. We conclude from this study that the increase in PLA2 activity seen in association with sepsis and septic shock results from a dramatic elevation in levels of a circulating PLA2 enzyme. This inflammatory PLA2 is indistinguishable, both immunologically and chemically, from that associated with rheumatoid arthritis. Therapeutic agents directed towards inhibition of this inflammatory PLA2 enzyme may have utility in the treatment of both chronic and acute inflammatory disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Parker, M. M., andJ. E. Parillo. 1983. Septic shock: Hemodynamics and pathogenesis.JAMA 250:3324–3327.

    Google Scholar 

  2. Shubin, H., andM. H. Weil. 1976. Bacterial shock.JAMA 235:421–424.

    Google Scholar 

  3. Kreger, B. E., D. E. Craven, andW. R. McCabe. 1980. Gram-negative bacteraemia. III. Reassessment of etiology, epidemiology and ecology in 612 patients.Am. J. Med. 63:332–343.

    Google Scholar 

  4. Kreger, B. E., D. E. Craven, andW. R. McCabe. 1980. Gram-negative bacteraemia. IV. Re-evaluation of clinical features and treatment in 612 patients.Am. J. Med. 68:344–355.

    Google Scholar 

  5. MacLean, L. D., W. G. Mulligan, A. P. H. McClean, andJ. H. Duff. 1967. Patterns of septic shock in man: a detailed study of 56 patients.Ann. Surg. 166:543–562.

    Google Scholar 

  6. Pollack, M. M., A. I. Fields, andU. E. Ruttimann. 1985. Distributions of cardiopulmonary variables in pediatric survivors and nonsurvivors of septic shock.Crit. Care. Med. 13:454–459.

    Google Scholar 

  7. Abraham, E., W. C. Shoemaker, R. D. Bland, andJ. C. Cobo. 1983. Sequential cardiorespiratory patterns in septic shock.Crit. Care. Med. 11:799–803.

    Google Scholar 

  8. Abraham, E., R. D. Bland, J. C. Cobo, andW. C. Shoemaker. 1984. Sequential cardiorespiratory patterns associated with outcome in septic shock.Chest 85:75–80.

    Google Scholar 

  9. Fein, A. M., M. Lippmann, H. Holtzman, A. Eliraz, andS. K. Goldberg. 1983. The risk factors, incidence, and prognosis of ARDS following septicaemia.Chest 83:40–42.

    Google Scholar 

  10. Kaplan, R. L., S. A. Sahn, andT. L. Petty. 1979. Incidence and outcome of the respiratory distress syndrome in gram-negative sepsis.Arch. Intern. Med. 139:867–869.

    Google Scholar 

  11. Colucci, M., J. A. Paramo, andD. Collen. 1985. Generation in plasma of a fast-acting inhibitor of plasminogen activator in response to endotoxin stimulation.J. Clin. Invest. 75:818–824.

    Google Scholar 

  12. Morrison, D. C., andJ. L. Ryan. 1987. Endotoxins and disease mechanisms.Annu. Rev. Med. 38:417–432.

    Google Scholar 

  13. Suffredini, A. F., P. C. Harpel, andJ. E. Parillo. 1989. Promotion and subsequent inhibition of plasminogen activation after administration of intravenous endotoxin to normal subjects.N. Engt. J. Med. 320:1165–1172.

    Google Scholar 

  14. Bendtzen, K. 1988. Interleukin 1, interleukin 6 and tumor necrosis factor in infection, inflammation and immunity.Immunol. Lett. 19:183–191.

    Google Scholar 

  15. Beutler, B., andA. Cerami. 1987. Cachectin: more than a tumor necrosis factor.N. Eng. J. Med. 316:379–385.

    Google Scholar 

  16. Clark, M. A., M. J. Chen, S. T. Crooke, andJ. S. Bomalaski. 1988. Tumour necrosis factor (cachectin) induces phospholipase A2 activity and the synthesis of a phospholipase A2activating protein in endothelial cells.Biochem. J. 250:125–132.

    Google Scholar 

  17. Heinrich, P. C., J. V. Castell, andT. Andus. 1990. Interieukin-6 and the acute phase response.Biochem. J. 265:621–636.

    Google Scholar 

  18. Stern, D. M., I. Bank, P. P. Nawroth, J. Cassimeris, W. Kiseil, W. Fenton II, C. Dinarello, L. Chess, andL. Jaffe. 1985. Self-regulation of procoagulant events on the endothelial cell surface.J. Exp. Med. 162:1223–1235.

    Google Scholar 

  19. Coalson, J. J. 1986. Pathology of sepsis, septic shock and multiple organ failure.In Perspective on Sepsis and Septic Shock. W. J. Sibbald and C. L. Sprung, editors. Society of Critical Care Medicine, Fullerton, California:27–59.

    Google Scholar 

  20. McGovern, V. J. 1984. Shock revisited.Pathol. Ann. 19:15–36.

    Google Scholar 

  21. Feuerstein, G., andJ. M. Hallenbeck. 1987. Prostaglandins, leukotrienes, and plateletactivating factor in shock.Annu. Rev. Pharmacol. Toxicol. 27:301–313.

    Google Scholar 

  22. Irvine, R. F. 1982. How is the level of free arachidonic acid controlled in mammalian cells?Biochem. J. 204:3–16.

    Google Scholar 

  23. Slotman, G. J., K. W. Burchard, J. J. Williams, A. D'arezzo, andS. A. Yellin. 1986. Interaction of prostaglandins, activated complement and granulocytes in clinical sepsis and hypotension.Surgery 99:744–750.

    Google Scholar 

  24. Vadas, P., andJ. B. Hay. 1983. Involvement of circulating phospholipase A2 in the pathogenesis of the hemodynamic change in endotoxin shock.Can. J. Physiol. Pharmacol. 61:561–566.

    Google Scholar 

  25. Vadas, P. 1984. Elevated plasma phospholipase A2 levels: Correlation with the hemodynamic and pulmonary changes in gram-negative septic shock in man.J. Lab. Clin. Med. 104:873–881.

    Google Scholar 

  26. Vadas, P., W. Pruzanski, E. Stefanski, B. Sternby, R. Mustard, J. Bohnen, I. Fraser, V. Farewell, andC. Bombardier. 1988. Pathogenesis of hypotension in septic shock: Correlation of circulatory phospholipase A2 levels with circulatory collapse.Crit. Care. Med. 16:1–6.

    Google Scholar 

  27. Seilhamer, J. J., T. L. Randell, M. Yamanaka, andK. L. Johnson. 1986. Pancreatic phospholipase A2: Isolation of the human gene and cDNAs from porcine pancreas and human lung.DNA 5:519–527.

    Google Scholar 

  28. Verkeij, H. M., A. J. Slotboom, andG. H. Dehaas. 1981. Structure and function of phospholipase A2.Rev. Physiol. Biochem. Pharmacol. 91:191–203.

    Google Scholar 

  29. Verkeij, H. M., J. Westerman, B. Sternby, andG. Dehaas. 1983. The complete primary structure of phospholipase A2 from human pancreas.Biochem. Biophys. Acta 747:93–99.

    Google Scholar 

  30. Hara, S., I. Kudo, H. Chang, K. Matsuta, T. Miyamoto, andK. Inoue. 1988. Amino acid composition and NH2-terminal amino acid sequence of human phospholipase A2 purified from rheumatoid synovial fluid.J. Biochem. 104:326–328.

    Google Scholar 

  31. Hara, S., I. Kudo, H. Chang, K. Matsuta, T. Miyamoto, andK. Inoue. 1989. Purification and characterisation of extracellular phospholipase A2 from human synovial fluid in rheumatoid arthritis.J. Biochem. (Tokyo) 105:395–399.

    Google Scholar 

  32. Lai, C., andK. Wada. 1988. Phospholipase A2 from human synovial fluid: Purification and structural homology to the placental enzyme.Biochem. Biophys. Res. Commun. 157:488–493.

    Google Scholar 

  33. Stefanski, E., W. Pruzanski, B. Sternby, andP. Vadas. 1986. Purification of a soluble phospholipase A2 from synovial fluid.J. Biochem. (Tokyo) 100:1297–1303.

    Google Scholar 

  34. Vadas, P., E. Stefanski, andW. Pruzanski. 1985. Characterisation of extracellular phospholipase A2 in rheumatoid synovial fluid.Life Sci. 36:579–578.

    Google Scholar 

  35. Seilhamer, J. J., W. Pruzanski, P. Vadas, S. Plant, J. A. Miller, J. Kloss, andL. K. Johnson. 1989. Cloning and recombinant expression of phospholipase A2 present in rheumatoid arthritic synovial fluid.J. Biol. Chem. 264:5335–5338.

    Google Scholar 

  36. Kramer, R. M., C. Hession, B. Johansen, C. Hession, B. Johansen, G. Hayes, P. McGray, E. P. Chow, R. Tizard, andR. B. Pepinsky. 1989. Structure and properties of a human non-pancreatic phospholipase A2.J. Biol. Chem. 254:5768–5775.

    Google Scholar 

  37. Vadas, P., andJ. B. Hay. 1980. The release of phospholipase A2 from aggregated platelets and stimulated macrophages of sheep.Life Sci. 26:1721–1729.

    Google Scholar 

  38. Takayama, K. I., S. Kudo, M. Hara, M. Murakami, K. Matsuta, T. Mijamoto, andK. Inoue. 1990. Monoclonal antibodies against human synovial phospholipase A2.Biochem. Biophys. Res. Commun. 167:1309–1315.

    Google Scholar 

  39. Suwa, Y., I. Kudo, A. Imaizumi, M. Okada, T. Kamimura, Y. Suzuki, H. W. Chong, S. Hora, andK. Inoue. 1990. Proteinaceous inhibitors of phospholipase A2 purified from inflammatory sites in rats.Proc. Natl. Acad. Sci. U.S.A. 87:2395–2399.

    Google Scholar 

  40. Buchler, M., A. Deller, P. Malfertheiner, H. O. Kleine, H. Wiedeck, W. Uhl, M. Samtner, H. Freiss, T. Nevalainen, andH. G. Beger. 1989. Serum phospholipase A2 in intensive care patients with peritonitis, multiple injury and necrotizing pancreatitis.Klin. Wochenschr. 67:217–221.

    Google Scholar 

  41. Hoffmann, G. E., andW. G. Guder. 1989. Serum phospholipase in regulatory and pathophysiological aspects.Klin. Wochenschr. 67:144–148.

    Google Scholar 

  42. Vadas, P., andW. Pruzanski. 1986. Role of secretory phospholipase A2 in the pathology of disease.Lab. Invest. 55:391–399.

    Google Scholar 

  43. Vadas, P., W. Pruzanski, andE. Stefanski. 1989. Phospholipase A2 in acute bacterial peritonitis in man.In Cell Activation and Signal Initiation. E. A. Dennis, T. Hunter, and M. Berridge, editors. Allan R. Liss, New York. 311–316.

    Google Scholar 

  44. Zalewski, A., S. Goldberg, andK. Maroko. 1988. The effects of phospholipase A2 inhibition on experimental infarct size, left ventricular hemodynamics and regional myocardial blood flow.Int. J. Cardiol. 21:247–257.

    Google Scholar 

  45. Chang, J., S. C. Gilman, andJ. A. Lewis. 1986. Interleukin-1 activates phospholipase A2 in rabbit chondrocytes: A possible signal for IL-1 action.J. Immunol. 136:1283–1287.

    Google Scholar 

  46. Godfrey, R. W., W. J. Johnson, andS. T. Hoffstein. 1988. Interleukin-1 stimulation of phospholipase activity in at synovial fibroblasts.Arthritis Rheum. 31:1421–1428.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Pacific Biotechnology Ltd., 74 McLachlan Ave, 2011, Rushcutters Bay, N.S.W., Australia

    Julie -Ann Green, Glenn M. Smith, Richard Buchta, Ivan A. Rajkovic & Kieran F. Scott

  2. Garvan Institute of Medical Research, 384 Victoria St., 2010, Darlinghurst, N.S. W., Australia

    Glenn M. Smith, Richard Lee, Ken Y. Ho, Ivan A. Rajkovic & Kieran F. Scott

  3. Intensive Care Unit, St. Vincent's Hospital, 2010, Darlinghurst, N.S.W., Australia

    Richard Lee

Authors
  1. Julie -Ann Green
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Glenn M. Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Richard Buchta
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Richard Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ken Y. Ho
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ivan A. Rajkovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kieran F. Scott
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Green, J.A., Smith, G.M., Buchta, R. et al. Circulating phospholipase A2 activity associated with sepsis and septic shock is indistinguishable from that associated with rheumatoid arthritis. Inflammation 15, 355–367 (1991). https://doi.org/10.1007/BF00917352

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00917352

Keywords

Search

Navigation