Skip to main content

Immunopharmacologic Aspects of Lipopolysaccharide Endotoxin Action with Special Reference to Cyclic Nucleotides

  • Chapter
Endotoxin

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 256))

Abstract

Lipopolysaccharides (LPS) are responsible for the immunopharmacologic activities of the endotoxins of gram-negative bacteria. This chapter will discuss their immunopharmacologic actions and the evidence that their actions are mediated in part by cyclic nucleotides. The lipopolysaccharides are ubiquitous in nature and have many immunomodulatory activities. As a result, many immunologists consider them ever present nuisances perturbing their experiments. Clearly in the context of endotoxemia and sepsis the toxicities of endotoxins on the body’s defense systems, including hyperpyrexia, intra-vascular coagulation. reticuloendothelial system (RES) blockade, etc., can be considered host destructive. On the other hand, in the absence of disease, low doses of endotoxins may be considered positive immunoregulatory contributing to more effective host defense. It is possible to envision them as being part of the host defense mechanism. It may be that the nonpathogenic gastrointestinal flora provides a continuous low level of LPS acting as hormonal signals to promote the development and enhance the function of the entire immune system. Endotoxins regulate, either directly or indirectly. almost every phase of the development and function of the natural and specific immune defense systems of the body. They generally promote growth and function of the cell populations involved. They do so at low concentrations (ng/ml), i.e., at concentrations which may be periodically, even regularly. achieved locally and perhaps also systemically. Finally, they appear to act via the cyclic nucleotide pathways by which many of the body’s hormones act and many of the molecules mediating immune function are also thought to act. They, therefore, qualify as messengers acting via receptors and hormonal pathways in physiologically constructive ways.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Apte, R., Hertogs, C. and Pluznik, D., 1980, Regulation of lipopolysaccharide-induced granulopoiesis and macrophage formation by spleen cells. J. Immunol. 124: 1223.

    PubMed  CAS  Google Scholar 

  2. Beckner, S. K. and Farrar, W. L., 1986, Interleukin 2 modulation of adenylate cyclase. J. Biol. Chem. 261: 3043.

    Google Scholar 

  3. Betel, I., Martijnse, J. and VandenBerg, K., 1974, Absence of an increase in phospholipid turnover in mitogen-stimulated B lymphocytes. Cell Immunol. 14: 2568.

    Article  Google Scholar 

  4. Bhatnager, R., Schade, U., Rietschel, E. and Decker, K., 1982, Involvement of prostaglandin E and adenosine 3’,5’-monophosphate in lipopolysaccharide-stimulated collagenase release by rat Kupffer cells. Eur. J. Biochem. 125: 125.

    Google Scholar 

  5. Bitensky, M. W., Gorman, R. E. and Thomas, L., 1971, Selective stimulation of epinephrine-responsive adenyl cyclase in mice by endotoxin. Proc. Soc. Biol. Med. 138: 773.

    Google Scholar 

  6. Bomboy, J. D., Jr. and Graber, S. E., 1980, Stimulation of cyclic 3’,5’guanosine monophosphate levels in rat spleen cells by lipopolysaccharide preparations. J. Lab. Clin. Med. 95: 654.

    Google Scholar 

  7. Bonney, R. J. and Humes, J. L., 1984, Physiological and pharmacological regulation of prostaglandin and leukotriene production by macrophages. J. Leuk. Biol. 35: 1.

    Google Scholar 

  8. Bourne, H. R., Lichtenstein, M., Melmon, K. L., Henney, C. S., Weinstein, Y. and Shearer, G. M., 1974, Modulation of inflammation and immunity by cyclic AMP. Science 184: 19.

    CAS  Google Scholar 

  9. Carswell, E. A., Old, L. J., Kassel, R. L., Green, S., Fiore, N. and Williamson, B., 1975, An endotoxin-induced serum factor that causes necrosis of tumors. Proc. Natl. Acad. Sci. 72: 3666.

    Google Scholar 

  10. Chen, S. S., Tung, J. S., Good, R. A. and Hadden, J. W., 1983, Changes in surface antigens of immature thymocytes under the influence of T cell growth factor and thymic factors. Proc. Natl. Acad. Sci. 80: 5980.

    Google Scholar 

  11. Coffey, R. G. and Hadden, J. W., 1982, Phorbol myristate acetate stimulation of lymphocyte guanylate cyclase and cyclic GMP phosphodiesterase and reduction of adenylate cyclase. Cancer Res. 43: 150.

    Google Scholar 

  12. Coffey, R. G. and Hadden, J. W., 1985, Neurotransmitters, hormones and cyclic nucleotides in lymphocyte regulation. Fed. Proc. 44: 112.

    Google Scholar 

  13. Coffey, R. G. and Hadden, J. W., 1985, Stimulation of lymphocyte guanylate cyclase by arachidonic acid and HETEs, in: “Prostaglandins, Leukotrienes, and Lipoxins,” J. M. Bailey, ed., Plenum Press, New York.

    Google Scholar 

  14. Cohen, Z. A. and Morse, S., 1960, Functional and metabolic properties of polymorphonuclear Leukocytes. II. The influence of a lipopolysaccharide endotoxin. J. Exp. Med. 111: 689.

    Google Scholar 

  15. Cook, J. A., Wise, W. C. and Halushka, P. V., 1981, Thromboxane A2 and prostacyclin production by lipopolysaccharide-stimulated peritoneal macrophages. J. Reticul. Soc. 30: 445.

    Google Scholar 

  16. DesPrez, R. M., 1964, Effects of bacterial endotoxin on rabbit platelets. IV. The divalent ion requirements of endotoxin induced and immunologically induced platelet injury. J. Exp. Med. 124: 971.

    Google Scholar 

  17. Djeu, J., Heinbaugh, J., Holden, H. and Herberman, R., 1979, Augmentation of mouse natural killer cell activity by interferon and interferon inducers. J. Immunol. 122: 175.

    PubMed  CAS  Google Scholar 

  18. Evans, D. J., Jr., Chen, C., Curlin, G. T. and Evans, D. G., 1972, Stimulation of adenyl cyclase by Escherichia coli enterotoxin. Nature New Biol. 236: 137.

    Article  PubMed  CAS  Google Scholar 

  19. Fairchild, S. and Cohen, J., 1978, B lymphocyte precursors, J. Immunol. 12: 1227.

    Google Scholar 

  20. Field, M., Graf, L. H., Jr., Laird, W. and Smith, P. L., 1978, Heat-stable enterotoxin of Escherichia coli: In vitro effects on guanylate cyclase activity, cyclic GMP concentration, and ion transport in small intestine. Proc. Natl. Acad. Sci. 75: 2800.

    Google Scholar 

  21. Forbes, J., Nakao, Y. and Smith, R., 1975, T mitogens trigger LPS responsiveness in mouse thymic cells. J. Immunol. 114: 1004.

    PubMed  CAS  Google Scholar 

  22. Freedman, M. H., 1979, Early biochemical events in lymphocyte activation. Cell Immunol. 44: 290.

    Article  PubMed  CAS  Google Scholar 

  23. Gery, I., Kruger, J. and Spiegel, S., 1972, Stimulation of B lymphocytes by endotoxin: Reactions of thymus-deprived mice and karyotypic analysis of dividing cells in mice bearing T6–T6 thymus grafts. J. Immunol. 108: 1088.

    PubMed  CAS  Google Scholar 

  24. Ghezzi, P., Saccardo, B. and Bianchi, M., 1986, Role of reactive oxygen intermediates in the hepatoxicity of endotoxin. Immunopharmacol. 12: 241.

    Article  CAS  Google Scholar 

  25. Graff, G., Stephenson, J. H., Glass, D. B., Haddox, M. K. and Goldberg, N. D., 1978, Activation of soluble splenic cell guanylate cyclase by prostaglandin endoperoxides and fatty acid hydroperoxides. J. Biol. Chem. 253: 7662.

    Google Scholar 

  26. Grugg, S. A. and Harmony, J. A. K., 1985, Increased phosphatidylinositol metabolism is an important but not an obligatory early event in B lymphocyte activation. J. Immunol. 134: 4087.

    Google Scholar 

  27. Hadden, E. M., Sadlik, J. R., Coffey, R. G. and Hadden, J. W., 1982, Effects of phorbol myristate acetate ( PMA) and lymphokine on cyclic GMP levels and proliferation of macrophages. Cancer Res. 42: 3064.

    Google Scholar 

  28. Hadden, J. W., Englard, A., Sadlik, J. R. and Hadden, E. M., 1979, The comparative effects of isoprinosine, levamisole, muramyl dipeptide and SM1213 on lymphocyte and macrophage proliferation and activation in vitro. Int. J. Immunopharmacol. 1: 17.

    Google Scholar 

  29. Hadden, J. W., and Coffey, R. G., 1982, Cyclic nucleotides in mitogen induced lymphocyte proliferation. Immunol. Today 3: 299.

    Google Scholar 

  30. Hadden, J. W., Galy, A., Hadden, E., Touraine, J-L. and Coffey. R., 1986. Cyclic nucleotides in the immunopharmacology of lipopolysaccharide endotoxins, in: “Immunobiology and Immunopharmacology of Bacterial Endotoxins,” A. Szentivanyi, H. Friedman, and A. Nowotny, eds., Plenum Press, New York.

    Google Scholar 

  31. Hadden, J. W., Specter, S., Galy, A., Touraine, J-L. and Hadden, E., 1986, Thymic hormones, interleukins, endotoxin and thymomimetic drugs in T lymphocyte ontogeny, in: “Advances in Immunopharmacology III,” L. Chedid, J. W. Hadden, F. Spreafico, P. Dukor and Willoughby, D., eds., Pergamon Press, Oxford.

    Google Scholar 

  32. Hadden, J. W., Hadden, E. M. and Coffey, R. G., 1987, Interleukin II increases cyclic GMP levels in immature thymocytes and mitogen-primed T lymphocytes. Int. J. Immunopharmacol. 9: 851.

    Google Scholar 

  33. Hadden, J. W., 1987, Transmembrane signals in the activation of T lymphocytes, in: “Mechanisms of Lymphocyte Activation and Immune Regulation,” S. Gupta, W. E. Paul, and A. S. Fauci, eds., Plenum Press, New York.

    Google Scholar 

  34. Hammerling, U., Chin, A. and Scheid, M., 1975, The ontogeny of murine B lymphocytes. J. Immunol. 115: 1425.

    PubMed  CAS  Google Scholar 

  35. Hazeki, K., Mori, Y., Ui, M., 1986, Induction of refractories of cyclic AMP responses to prostaglandin El and epinephrine by prior exposure of guinea pig macrophages to lipopolysaccharide. Arch. Biochem. Biophys. 246: 772.

    Google Scholar 

  36. Hoffman, M., Weiss, O., Koenig, S., Hirst, J. and Oettgen, H., 1975, Suppression and enhancement of the T cell dependent production of anti-body to SRBC in vitro by bacterial lipopolysaccharide. J. Immunol. 114: 738.

    Google Scholar 

  37. Hoffman, M., Galanos, C., Koenig, S. and Oettgen, H., 1977, B cell activation by lipopolysaccharide. J. Exp. Med. 146: 1640.

    Google Scholar 

  38. Katz, S., Kierszenbaum, F. and Waksman, B., 1978, Mechanisms of action of lymphocyte-activating factor. J. Immunol. 121: 2386.

    Google Scholar 

  39. Kurland, J. and Bockman, R., 1978, Prostaglandin E production by human blood monocytes and mouse peritoneal macrophages. J. Exp. Med. 147: 952.

    Google Scholar 

  40. Largen, M. T. and Votta, B., 1983, Immunocytochemical evidence for 3’,5’-cGMP and 3’,5’-cGMP-dependent protein kinase involvement in lymphocyte proliferation. J. Cyclic Nucleo. Prot. Phosphoryl. Res. 9: 231.

    Google Scholar 

  41. Luderitz, O., Schade, U., Rietschel, E. Th., 1986, Formation and metabolism of leukotriene C4 in macrophages exposed to bacterial lipopolysaccharide. Eur. J. Biochem. 155: 377.

    Google Scholar 

  42. Lui, M-S., Ghosh, S. and Yang, Y., 1983, Change in membrane lipid fluidity induced by phospholipase A activation: A mechanism of endotoxin shock. Life Sci. 33: 1995.

    Google Scholar 

  43. Melchers, F. and Anderson, J., 1974, IgM in bone marrow-derived lymphocytes. Eur. J. Immunol. 4: 181.

    Google Scholar 

  44. Moore, R. N., Urbacek, R., Wahl, L. M. and Mergenhagen, S. E., 1979, Prostaglandin regulation of colony-stimulation factor production by lipopolysaccharide stimulated murine leukocyte. Infect. Immun. 26: 408.

    Google Scholar 

  45. Morris, D. D. and Moore, J. N., 1987, Endotoxin-induced production of thromboxane and prostacyclin by equine peritoneal macrophages. Circ. Shock 23: 295.

    Google Scholar 

  46. Naylor, P. Camp, C. Phillips, A., Thurman, G. and Goldstein, A., 1978, Effect of thymosin and lipopolysaccharide on murine lymphocyte cyclic AMP. J. Immunol. Meth. 20: 143.

    Google Scholar 

  47. Nishizuka, Y., 1984, The role of protein kinase C in cell surface signal transduction and tumor promotion. Nature 308: 693.

    Article  PubMed  CAS  Google Scholar 

  48. Nowotny, A., 1983, “Beneficial Effects of Endotoxin,” Plenum Press, New York.

    Google Scholar 

  49. Ohara, J. and Watanabe, T., 1982, Microinjection of macromolecules into normal murine lymphocytes by cell fusion techniques. J. Immunol. 128: 1090.

    PubMed  CAS  Google Scholar 

  50. Oppenheim, J., Koopman, W., Wahl, L. and Dougherty, glandin S., 1980, Prosta-produced by activa-murine E2 rather than lymphocyte-activating factor ted human mononuclear cells stimulates increases in cAMP. Cell Immunol. 49: 64.

    Article  PubMed  CAS  Google Scholar 

  51. Ozato, K., Adler, W. and Ebert, J., 1975, Synergism of bacterial lipopolysaccharide and concanavalin A in the activation of thymic lymphocytes. Cell Immunol. 17: 532.

    Article  PubMed  CAS  Google Scholar 

  52. Peavy, D. L. and Fairchild, E. J., 1986, II, Evidence for lipid peroxidation in endotoxin-poisoned mice. Infect. Immun. 52: 613.

    Google Scholar 

  53. Rochette-Egly, C. and Tovey, M. G., 1982, Interferon enhances guanylate cyclase activity in human lymphoma cells. Biochem. Biophysica. Res. Commun. 107: 105.

    Google Scholar 

  54. Russell, S. W., 1986, Involvement of endotoxin in macrophage activation for antitumor immunity, in: “Immunobiology and Immunopharmacology of Bacterial Endotoxins,” A. Szentivanyi, H. Friedman, and A. Nowotny, eds., Plenum Press, New York.

    Google Scholar 

  55. Schade, U. F., 1986, Involvement of lipoxygenases in the activation of mouse macrophages by endotoxin. Biochem. Biophys. Res. Commun. 138: 842.

    Google Scholar 

  56. Scheid, M., Hoffmann, M., Komuro, K., Hemmerlin, U., Abbott, J., Boyse, E., Cohen, G., Hooper, J., Schulof, R. and Goldstein, A., 1973, Differentiation of T cells induced by preparations from thymus and by nonthymic agents. J. Exp. Med. 138: 1027.

    Google Scholar 

  57. Scheid, M. P., Goldstein, G. and Boyse, E. A., 1978, The generation and regulation of lymphocyte populations. J. Exp. Med. 147: 1727.

    Google Scholar 

  58. Schmidtke, J. and Najarian, J., 1975, Synergistic effects on DNA synthesis of phytohemagglutinin or concanavalin A and lipopolysaccharide in human peripheral blood lymphocytes. J. Immunol. 114: 742.

    PubMed  CAS  Google Scholar 

  59. Shenker, B. J. and Gray, I., 1979, Cyclic nucleotide metabolism during lymphocyte transformation. I. Cell. Immunol. 43: 11.

    Google Scholar 

  60. Shenker, B. J. and Gray, I., 1979, Cyclic nucleotide metabolism during lymphocyte transformation. II. Cell. Immunol. 43: 23.

    Google Scholar 

  61. Strauss, B. S. and Stetson, C. A., 1960, Studies on the effect of certain leukocytes of peripheral blood. J. Exp. Med. 112: 653.

    Google Scholar 

  62. Szentivanyi, A., Friedman, H. and Nowotny, A., “Immunobiology and Immunopharmacology of Bacterial Endotoxins,” Plenum Press, New York.

    Google Scholar 

  63. Tsien, W-H., Sampson, M. and Sheppard, H., 1981, The elevation of mouse thymus cell cyclic adenosine monophosphate (cAMP) by lipopolysaccharide. Immunopharm. 3: 253.

    Article  CAS  Google Scholar 

  64. VanOosterhout, A. J. M., TenHave, G. A. M. and Nijkamp, F. P., 1986, Endotoxin-induced reduction of ß-adrenoceptor number in guinea pig splenic lymphocyte membranes. Agents Actions 19: 361.

    Article  CAS  Google Scholar 

  65. Vogel, S., Hilfiker, M. and Caulfield, M., 1983, Endotoxin-induced T-lymphocyte proliferation. J. Immunol. 130: 1774.

    Google Scholar 

  66. Watson, J., 1975, The influence of intracellular levels of cyclic nucleotides on cell proliferation and the induction of antibody synthesis. J. Exp. Med. 141: 97.

    Google Scholar 

  67. Watson, J., 1976, The involvement of cyclic nucleotide metabolism in the initiation of lymphocyte proliferation induced by mitogens. J. Immunol. 117: 1656.

    PubMed  CAS  Google Scholar 

  68. Watson, J., 1977, Involvement of cyclic nucleotides as intracellular mediators in the induction of antibody synthesis, in: “Comprehensive Immunology,” R. A. Good and S. B. Day, eds., Plenum Press, New York.

    Google Scholar 

  69. Watson, J., Epstein, R. and Cohn, M., 1973, Cyclic nucleotides as intra-cellular mediators of the expression of antigen-sensitive cells. Nature 246: 404.

    Article  Google Scholar 

  70. Weissman, G. and Thomas, L., 1964, On a mechanism of tissue damage by bacterial endotoxins, in: “Bacterial Endotoxin,” M. Landy and W. Braun, eds., Rutgers University Press, New Brunswick.

    Google Scholar 

  71. Wrightman, P. and Raetz, C., 1984, The activation of protein kinase C by biologically active lipid moieties of lipopolysaccharide. J. Biol. Chem. 259: 1048.

    Google Scholar 

  72. Williamson, S., Wannemuehler, M., Kirillo, E., Pritchard, D., Michalek, S. and McGhee, J., 1984, LPS regulation of the immune response: separate mechanisms for murine B cell activation by lipid A (direct) and polysaccharide (macrophage-dependent) derived from bacteroide LPS. J. Immunol. 133: 2294.

    PubMed  CAS  Google Scholar 

  73. Winchurch, R. A., Hilberg, C., Birmingham, W. and Munster, A., 1982, Lipopolysaccharide-induced activation of suppressor cells: reversal by an agent which alters cyclic nucleotide metabolism. Immunol. 45: 147.

    CAS  Google Scholar 

  74. Wood, D. and Cameron, P., 1976, Stimulation of the rlease of a B cell activating factor from human monocytes. Cell. Immunol. 21: 133.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1990 Springer Science+Business Media New York

About this chapter

Cite this chapter

Hadden, J.W. (1990). Immunopharmacologic Aspects of Lipopolysaccharide Endotoxin Action with Special Reference to Cyclic Nucleotides. In: Friedman, H., Klein, T.W., Nakano, M., Nowotny, A. (eds) Endotoxin. Advances in Experimental Medicine and Biology, vol 256. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-5140-6_33

Download citation

  • DOI: https://doi.org/10.1007/978-1-4757-5140-6_33

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4757-5142-0

  • Online ISBN: 978-1-4757-5140-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics