Skip to main content
SpringerLink
Log in

Effect of bacterial endotoxin on lipoxygenase and cyclo-oxygenase metabolites by rat neutrophils and correlation with cellular functional parameters

  • Original Papers
  • Published:
Research in Experimental Medicine

Summary

The effect ofSalmonella enteritidis endotoxin on in vitro rat neutrophil cyclo-oxygenase and lipoxygenase metabolism, phagocytic activity, superoxide (O -2 ) generation, and microbicidal activity was investigated. Incubation of polymorphonuclear leukocytes (PMN) with 5, 25, and 50 µg of endotoxin significantly enhanced synthesis of immunoreactive (i) leukotriene (LT)C4/D4 and thromboxane (Tx)B2 (P < 0.001) as compared to control cells. Endotoxin 5 µg/ml produced optimal stimulation of the arachidonic acid metabolites. Calcium ionophore, A23187, significantly enhanced iLTC4/D4 and iTxB2 synthesis more than that elicited with endotoxin. Although phagocytic function was not significantly altered by endotoxin, intracellular killing ofC. albicans demonstrated enhanced microbicidal activity at 5 µg/ml of endotoxin. Superoxide generation was significantly enhanced in neutrophils stimulated with phorbol myristate acetate (PMA). Endotoxin (5 µg/ml) further potentiated superoxide generation by these cells when stimulated by PMA. These findings demonstrate that endotoxin directly enhances neutrophil iLTC4/D4 and iTxB2 synthesis. The enhanced arachidonic acid metabolism elicited by endotoxin in these cells parallels increased microbicidal activity and superoxide generation.

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. Aderen AA, Cohen DS, Whright SD, Cohn ZA (1985) Bacterial lipopolysaccharides prime macrophages for enhanced release of arachidonic acid metabolites. J Exp Med 164:165–179

    Google Scholar 

  2. Anderegg K, Anzeveno P, Cook JA, Halushka PV, McCarthy J, Wagner E, Wise WC (1983) Effects of a pyridine derivative thromboxane synthetase inhibitor and its inactive isomer in endotoxic shock in the rat. Br J Pharmacol 78:725–732

    PubMed  Google Scholar 

  3. Anderson FL, Jubiz W, Tsgaris TJ, Juida M (1975) Endotoxin-induced prostaglandin E and F release in dogs. Am J Physiol 223:410–414

    Google Scholar 

  4. Ball HA, Parrat JR (1983) Thromboxane and the pulmonary response to endotoxin in the cat. Circ Shock 10:263

    Google Scholar 

  5. Ball HA, Cook JA, Spicer KM, Halushka PV (1985) LY171883, a leukotriene D4/E4 antagonist attenuates leak in oleic acid induced pulmonary injury. Circulation 72:106

    Google Scholar 

  6. Ball HA, Cook JA, Spicer KM, Wise WC, Halushka PV (1986) Potential role of leukotrienes in oleic acid-induced pulmonary injury: Effects of essential fatty acid deficiency. Circ Shock 18:377

    Google Scholar 

  7. Bottoms GD, Johnson M, Ward D, Fessler J, Lamar C, Turek J (1986) Release of eicosanoids from white blood cells, platelets, smooth muscle cells, and endothelial cells in response to endotoxin and A23187. Circ Shock 20:25–34

    PubMed  Google Scholar 

  8. Bowers GJ, McVittie TJ, Hirsh EF, Conklin JC, Nelson RD, Roethel RJ, Fink MP (1985) Prostanoid production by lipopolysaccharide-stimulated Kupffer cells. J Surg Res 38:501–508

    PubMed  Google Scholar 

  9. Bremm KD, Brom J, Konig W, Spur B, Crea A, Bhakdi S, Lutz S, Fehrench FJ (1983) Generation of leukotrienes and lipoxygenase factors from human polymorphonuclear granulocytes during bacterial phagocytosis and interaction with bacterial exotoxins. Zentral Bakteriol Hyg I A 254:500

    Google Scholar 

  10. Bremm KD, Konig W, Spur B, Crea A, Galanos C (1984) Generation of slow-reacting substance (leukotrienes) by endotoxin and lipid A from human polylmorphonuclear granulocytes. Immunology 53:299–305

    PubMed  Google Scholar 

  11. Brigham KI, Duke SS (1985) Prostaglandins in lung disease: adult respiratory distress syndrome. Semin Respir Med 7:11–16

    Google Scholar 

  12. Burch RM, Knapp DR, Haluska PV (1979) Vasopressin stimulates thromboxane synthesis in the toad urinary bladder: Effects of imidazole. J Pharmacol Exp Ther 210:344–348

    PubMed  Google Scholar 

  13. Cook JA, Wise WC, Halushka PV (1980) Elevated thromboxane levels in the rat during endotoxic shock: Protective effects of imidazole, 13-azaprostanoic acid or essential fatty acid deficiency. J Clin Invest 65:227–230

    PubMed  Google Scholar 

  14. Cook JA, Wise WC, Halushka PV (1981b) Thromboxane A2 and prostacyclin production by lipopolysaccharide stimulated peritoneal macrophages. Reticuloendothel Soc 29:445

    Google Scholar 

  15. Cook JA, Rogers TS, Wise WC, Halushka PV (1985) Agents which modulate reticuloendothelial function and affect endotoxin sensitivity. In: Berry LJ (ed) Handbook of endotoxin, vol 3. Elsevier, Amsterdam Oxford New York, pp 303–339

    Google Scholar 

  16. Cook JA, Wise WC, Halushka PV (1985) Protective effect of a selective leukotriene antagonist in endotoxin shock in the rat. J Pharmacol Exp Ther 235:470–474

    PubMed  Google Scholar 

  17. Furukawa M, Yoshimoto T, Ochi K, Yamamoto S (1984) Studies on arachidonate 5-lipoxygenase of rat basophilic leukemia cells. Biochim Biophys Acta 795:458–465

    PubMed  Google Scholar 

  18. Hagmann W, Keppler D (1982) Leukotriene antagonists prevent endotoxin lethality. Naturwissenschaften 69:594–595

    PubMed  Google Scholar 

  19. Hagmann W, Denzliger C, Keppler D (1985) Production of peptide leukotrienes in endotoxin shock. FEBS Lett 180:309–313

    PubMed  Google Scholar 

  20. Halushka PV, Cook JA, Wise WC (1983) Beneficial effects of UK37248, a thromboxane synthetase inhibitor, in experimental endotoxic shock in the rat. Br J Clin Pharmacol 15:133S-139S

    PubMed  Google Scholar 

  21. Harlan J, Winn R, Hildebrands J, Harker L (1983) Selective inhibition of thromboxane synthesis during experimental endotoxemia in the goat: Effects on pulmonary haemodynamics and lung lymph flow. Br J Clin Pharmacol 15:123S-126S

    PubMed  Google Scholar 

  22. Harris RH, Zmudka M, Madolox Y, Ramwell PW, Fletcher JR (1980) Relationship of TxB2 and 6-Keto-PGF1α to the hemodynamic changes during baboon endotoxic shock. In: Samuelson B, Ramwell PW, Padetti R (eds) Adv Prostaglandin Thromboxane Res. Raven Press, New York 7, p 843

    Google Scholar 

  23. Hayes EC, Lombardo DL, Girard Y, Maycock AL, Rokach J, Rosenthal AS, Young RN, Egan RW, Zweernich HJ (1983) Measuring leukotrienes of slow reacting substance of anaphylaxis: Development of a specific radioimmunoassay. J Immunol 131:429–433

    PubMed  Google Scholar 

  24. Hofman SL, Majerus PW (1982) Identifcation and properties of two distinct phosphatidylinsitol-sepcific phospholipase c enzymes from sheep seminal vesicular glands. J Biol Chem 257:6461–6469

    PubMed  Google Scholar 

  25. Humes JL, Sadowski S, Glavage M, Goldenberg M, Subers E, Bonney RJ, Kuehl FA (1982) Evidence for two sources of arachidonic acid for oxidative metabolism by mouse peritoneal macrophages. J Biol Chem 257:1591–1594

    PubMed  Google Scholar 

  26. Johnston RB, Gozdik CA, Cohn ZA (1978) Increased superoxide anion production by immunologically activated and chemically elicited macrophages. J Exp Med 160:1656–1671

    Google Scholar 

  27. Kitchen EA, Dawson W (1984) Comparative effects of inhibitors of the lipoxygenase enzyme system on leukocyte chemiotaxis. J Pharm Pharmacol 36:300–304

    PubMed  Google Scholar 

  28. Luderitz T, Shade U, Rietshel ET (1986) Formation and metabolism of leukotriene C4 in macrophages exposed to bacterial lipopolysaccharide. Eur J Biochem 155:377–382

    PubMed  Google Scholar 

  29. Meyrick B (1986) Endotoxin-mediated pulmonary endothelial cell injury. Fed Proc 45:19–24

    PubMed  Google Scholar 

  30. Ochi K, Yoshimoto T, Yamamoto S (1983) Arachidonate 5-lipoxygenase of guinea pig peritoneal polymorphonuclear leukocytes. J Biol Chem 258:5754–5758

    PubMed  Google Scholar 

  31. Rogers TS, Halushka PV, Wise WC, Cook JA (1986) Differential alteration of lipoxygenase and cylco-oxygenase metabolism by rat peritoneal macrophages induced by endotoxin tolerance. Prostaglandins 31:639–650

    PubMed  Google Scholar 

  32. Saija A, Matera G, Trimarchi GR, Altavilla D, Focà A, Costa G, Mastroeni P, Caputi AP (1985) Sulphasalazine reduces thromboxane B2 synthesis induced by experimental endotoxic shock in the rat. IRCS Med Sci 13:26

    Google Scholar 

  33. Smith DL, Rommel FJ (1977) A rapid micromethod for the simultaneous determination of phagocytic and microbicidal activity of human peripheral blood leukocytes in vitro. J Immunol Methods 17:241–247

    PubMed  Google Scholar 

  34. Spagnuolo PJ, Ellner JJ, Hassid A, Dunn HJ (1980) Thromboxane A2 mediators augmented polymorphonuclear leukocytes adhesiveness. J Clin Invest 66:406–414

    PubMed  Google Scholar 

  35. Tempel GE, Etemadi AR, Wise WC, Halushka PV (1986) Improvment in cardiovascular (c.v.) function in endotoxin (LPS) shock by the leukotriene (LT) antagonist. LY171883. Circ Shock 18:348–349

    Google Scholar 

  36. Tripp CS, Mahoney M, Needelman P (1985) Calcium ionophore enables soluble agonists to stimulate macrophage 5-lipoxygenase. J Biol Chem 260:5895–5898

    PubMed  Google Scholar 

  37. Ward PA, Sulawik MC, Johnson KJ (1984) Rat neutrophil activation and effects of lipoxygenase and cyclo-oxygenase inhibitors. Am J Pathol 116:223–233

    PubMed  Google Scholar 

  38. Wise WC, Cook JA, Halushka PV, Knapp DR (1980) Protective effects of thromboxane synthetase inhibitors in rats in endotoxic shock. Circ Res 46:854–859

    PubMed  Google Scholar 

  39. Worthen GS, Haslett C, Smedly LA, Rees AJ, Gumbay RS, Henson JE, Henson PM (1986) Lung vascular injury induced by chemotactic factors: Enhancment by bacterial endotoxins. Fed Proc 45:7–12

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Medical Microbiology, University of Messina, Piazza XX Settembre 4, I-98100, Messina, Italy

    D. Altavilla & M. C. Berlinghieri

  2. Institute of Medical Microbiology, University of Reggio Calabria, Italy

    A. Focà

  3. Dept. of Physiology, Medical University of South Carolina, Charleston, SC, USA

    J. A. Cook

Authors
  1. D. Altavilla
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. C. Berlinghieri
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Focà
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. A. Cook
    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

Altavilla, D., Berlinghieri, M.C., Focà, A. et al. Effect of bacterial endotoxin on lipoxygenase and cyclo-oxygenase metabolites by rat neutrophils and correlation with cellular functional parameters. Res. Exp. Med. 188, 9–17 (1988). https://doi.org/10.1007/BF01852089

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01852089

Key words

Search

Navigation