Beneficially Active Structural Entities in Endotoxin Preparations

  • Alois Nowotny
Part of the University of South Florida International Biomedical Symposia Series book series (EMISS, volume 18)

Abstract

The effects of endotoxin preparations can be divided into two large groups. One consists of reactions which are harmful and may lead to irreversible vascular collapse, shock and death. The other covers those which are beneficial, such as enhanced immune responsiveness, elevated non-specific resistance to microbial infections including fungi and viruses, increased leukopoiesis, activation of lymphocytes and of the functions of macrophages as well as of the entire reticuloendothelial system. Finally, one should mention the anti-tumor effects of endotoxins on some established animal malignancies and the resistance enhancement to transplantable experimental tumors induced by endotoxin. Table 1 shows some of those endotoxic effects which may be considered as beneficial.

Keywords

Hydrolysis Toxicity Polysaccharide Electrophoresis Pyridine 

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References

  1. 1.
    A. M. Abdelnoor, H. L. Chang, P. H. Pham, and A. Nowotny, Lack of relationship between toxicity and bone marrow cell colony stimulating activity of endotoxin preparations, Proc. Soc. Exp. Biol. Med. 163: 15 (1980).PubMedGoogle Scholar
  2. 2.
    R. L. Anacker, R. A. Finkelstein, W. T. Haskins, M. Landy, K. C. Milner, E. Ribi, and R. W. Stashak, Origin and properties of naturally occurring hapten from Escherichia coli, J. Bacteriol. 88: 1705 (1964).PubMedGoogle Scholar
  3. 3.
    U. H. Behling, Alterations of survival and immunity in normal and irradiated mice treated with bacterial endotoxin and its derivatives, Ph.D. Thesis, Temple University, Philadelphia, Pennsylvanyia (1975).Google Scholar
  4. 4.
    U. H. Behling and A. Nowotny, Immune adjuvancy of lipopolysaccharide and a nontoxic hydrolytic product demonstrating oscillating effects with time, J. Immunology 118: 1905 (1977).Google Scholar
  5. 5.
    U. H. Behling and A. Nowotny, Long-term adjuvant effect of bacterial endotoxin in prevention and restoration of radiation-caused immunosuppression, Proc. Soc. Exp. Biol. Med. 157: 348 (1978).PubMedGoogle Scholar
  6. 6.
    U. H. Behling, P. H. Pham, F. Madani, and A. Nowotny, Components of lipopolysaccharide which induce colony stimulation, adjuvancy and radioprotection, in: “Microbiology 1980,” D. Schlessinger, ed., American Society of Microbiology, Washington, D.C. (1980).Google Scholar
  7. 7.
    U. H. Behling and A. Nowotny, Cyclic changes of positive and negative effects of single endotoxin injection, in: “Bacterial Endotoxins and Host Response,” M. K. Agarwal, ed., Elsevier/North-Holland Biomedical Press (1980).Google Scholar
  8. 8.
    U. H. Behling and A. Nowotny, Bacterial endotoxins as modulators of specific and non-specific immunity, in: “Regulatory Implication of Oscillatory Dynamics in the Immune Response,” J. Hiernaux and C. DeLisi, eds., CRC Press (1982).Google Scholar
  9. 9.
    F. M. Berger, The effect of endotoxin on resistance to infections and disease, Adv. Pharmacol 5: 19 (1967).PubMedCrossRefGoogle Scholar
  10. 10.
    F. M. Berger, G. M. Fukui, B. J. Ludwig, and J. P. Rosselet, Increase of non-specific resistance to infection by Protodyne, a protein component derived from bacterial protoplasm, Proc. Soc. Exp. Biol. Med. 127: 556 (1968).PubMedGoogle Scholar
  11. 11.
    A. Boivin, J. Mesrobeanu, and L. Mesrobeanu, Extraction d’un complexe toxique et antigenique a partir du bacille dT Aertrycke, Compt. Rend. Soc. Biol. 114: 307 (1933).Google Scholar
  12. 12.
    C. E. Bulawa and C.R.H. Raetz, The biosynthesis of gram negative endotoxin: identification and function of UDP-2, 3-Diacylglucosamine in Escherichia coli, J. Biol. Chem. 259: 4846 (1984).PubMedGoogle Scholar
  13. 13.
    R. C. Butler and A. Nowotny, Combined immunostimulation in the prevention of tumor take in mice using endotoxins, their derivatives and other immune adjuvants, Cancer Immunol. Immunother. 6: 255 (1979).CrossRefGoogle Scholar
  14. 14.
    H. Chang, J. J. Thompson, and A. Nowotny, Release of colony stimulating factor (CSF) by non-endotoxic breakdown products of bacterial lipopoly- saccharides, Immunol. Commun. 3: 401 (1974).Google Scholar
  15. 15.
    C. M. Change and A. Nowotny, Relation of structure to function in bacterial O-antigens. VII. The biological activity of “lipid A” preparations, Immunochemistry 12: 19 (1975).CrossRefGoogle Scholar
  16. 16.
    J. Choay and M. Sakouhi, Fraction capable of inducing in vivo a resistance to bacterial infections, process for obtaining said fraction from bacteria and drugs containing said fraction, U.S. Patent 4, 148, 877.Google Scholar
  17. 17.
    M. J. Crutchley, D. G. Marsh, and J. Cameron, Biological studies on free endotoxin and a non-toxic material from culture supernatant fluids of Escherichia coli 078K80 (1968).Google Scholar
  18. 18.
    K. R. Cundy and A. Nowotny, Quantitative comparison of toxicity parameters of bacterial endotoxins, Proc. Soc. Exptl. Biol. Med. 127: 999 (1968).Google Scholar
  19. 19.
    S. Frank, S. Specter, A. Nowotny, and H. Friedman, Immunocyte stimulation in vitro by nontoxic bacterial lipopolysaccharide derivatives, J. Immunol. 119: 855 (1977).PubMedGoogle Scholar
  20. 20.
    G. G. Freeman and J. St. L. Philpot, The preparation and properties of a specific polysaccharide from Bact. typhosum Ty2, Biochem J. 36: 340 (1942). 1Google Scholar
  21. 21.
    R. C. Goldman and L. Leive, Heterogeneity of antigenic side chain length in LPS from Escherichia coli 0111 and Salmonella typhimurium LT2, Eur. J. Bioch 107: 145 (1980).CrossRefGoogle Scholar
  22. 22.
    N. Haeffner-Cavaillon, J. M. Cavaillon, and L. Szabo, Macrophage dependent polyclonal activation of splenocytes by Bordetella pertussis endotoxin and its isolated polysaccharide and lipid A region, Cell Immunol. 74: 1 (1982).PubMedCrossRefGoogle Scholar
  23. 23.
    N. Haeffner-Cavaillon, J. M. Cavaillon, M. Moreau, and L. Szabo, Interleukin secretion by human monocytes stimulated by the isolated polysaccharide region of Bordetella pertussis endotoxin, Mol. Immunol 21: 389 (1984).PubMedCrossRefGoogle Scholar
  24. 24.
    N. Haeffner-Cavaillon, J. M. Cavaillon, and L. Szabo, Cellular receptors for endotoxin, in: “Handbook of Endotoxin,” Volume 3, L. J. Berry, ed., Elsevier-North Holland Publishers, Amsterdam and New York (1985).Google Scholar
  25. 25.
    P. J. Hitchcock and T. M. Brown, Morphological heterogeneity among Salmonella lipopolysaccharide chemotypes in silver-stain polyacrylamide gels, J. Bacteriol. 154: 269 (1983).PubMedGoogle Scholar
  26. 26.
    A. G. Johnson and A. Nowotny, Relationship of structure to function in bacterial O-antigens. III. Biological properties of endotoxoids, J. Bact. 87: 809 (1964).PubMedGoogle Scholar
  27. 27.
    N. Kasai and A. Yamano, Studies of the lipids of endotoxins. Thin layer chromatography of lipid fractions, Jap. Exp. Med. 34: 329 (1964).Google Scholar
  28. 28.
    S. Lehrer and A. Nowotny, Isolation and purification of endotoxin by hydrolytic enzymes, Inf. and Imm. 6: 928 (1972).Google Scholar
  29. 29.
    D. G. Marsh and M. J. Crutchley, Purification and physico-chemical analysis of fractions from the culture supernatant of Escherichia coli 078K80: free endotoxin and a non-toxic fraction, Gen. Microbiol 47: 405 (1967).CrossRefGoogle Scholar
  30. 30.
    H. Mayer and J. Weckesser, “Unusual” lipid Afs structures, taxonomical relevance and potential value for endotoxin research, in: “Handbook of Endotoxin,” Vol. 1, E. Rietschel, ed., Elsevier Publishing, Amsterdam and New York (1984).Google Scholar
  31. 31.
    D. C. Morrison, S. J. Betz, and D. M. Jacobs, Isolation of a lipid A bound polypeptide responsible for “LPS-initiated” mitogenesis of C3H/HeJ spleen cells, J. Exp. Med. 144: 840 (1976).PubMedCrossRefGoogle Scholar
  32. 32.
    A. R. Kg, C. M. Chang, G. H. Chen, and A. Nowotny, Comparison of the chemical structure and biological activities of the glycolipids of Salmonella minnesota R595 and Salmonella typhimurium SL1102., Inf. and Immun. 10: 938 (1974).Google Scholar
  33. 33.
    M. Nishijima and C.R.H. Raetz, Membrane lipid biogenesis in Escherichia coli: identification of genetic loci for phosphotidylglycerol, J. Biol. Chem. 254: 7837 (1979).PubMedGoogle Scholar
  34. 34.
    A. Nowotny, Chemical structure of a phosphomucolipid and its occurrence in some strains of Salmonella, Am. Chem. Soc. 83: 501 (1961).CrossRefGoogle Scholar
  35. 35.
    A. Nowotny, Endotoxoid preparations, Nature 197: 721 (1963a).PubMedCrossRefGoogle Scholar
  36. 36.
    A. Nowotny, Relation of structure to function in bacterial O-antigens. II. Fractionation of lipids present in Boivin-type endotoxin of Serratia marcescens, J. Bact. 85: 427 (1963b).PubMedGoogle Scholar
  37. 37.
    A. Nowotny, Chemical detoxification of bacterial endotoxins, in: “Bacterial Endotoxins,” M. Landy and W. Braun, eds., Rutgers University Press, New Brunswick, NJ (1964).Google Scholar
  38. 38.
    A. Nowotny, Relation of chemical structure to pathologic activity of endotoxins, in: “Shock and Hypotension,” L. J. Mills and J. H. Moyer, eds., Grune and Stratton, Inc., New York (1965).Google Scholar
  39. 39.
    A. Nowotny, Heterogeneity of endotoxic bacterial lipopolysaccharides revealed by ion exchange column chromatography, Nature 210: 278 (1966).PubMedCrossRefGoogle Scholar
  40. 40.
    A. Nowotny, Molecular aspects of endotoxic reactions, Bact. Rev. 33: 72 (1969).PubMedGoogle Scholar
  41. 41.
    A. Nowotny, Chemical and biological heterogeneity of endotoxins, in: “Microbial Toxins,” Vol. IV, Weinbaum et al., eds., Academic Press, New York (1971a).Google Scholar
  42. 42.
    A. Nowotny, Relationship of structure and biological activity of bacterial endotoxins, Naturwissenschaften 58: 397 (1971b).PubMedCrossRefGoogle Scholar
  43. 43.
    A. Nowotny, Relation of structure to function in bacterial endotoxins, in: “Microbiology 1977, ” D. Schlessinger, ed., American Society of Microbiology, Washington, D.C. (1977).Google Scholar
  44. 44.
    A. Nowotny, “Basic Exercises in Immunochemistry,” 2nd Edition, Springer-Verlag, New York, Heidelberg, Berlin (1979).Google Scholar
  45. 45.
    A. Nowotny, Heterogeneity of endotoxins, in: “Handbook of Endotoxins,” Vol. 1, E. T. Rietschel, ed., Elsevier, Amsterdam and New York (1984).Google Scholar
  46. 46.
    A. M. Nowotny, S. Thomas, O. S. Duron, and A. Nowotny, Relations of structure to function in bacterial O-antigens. I. Isolation methods, J. Bact 85: 418 (1963).PubMedGoogle Scholar
  47. 47.
    A. Nowotny, K. Cundy, N. Neale, A. M. Nowotny, R. Radvany, S. Thomas, and D. Tripodi, Relation of structure to function in bacterterial O-antigens. IV. Fractionation of the components, Ann. N.Y. Acad. Sci. 133: 586 (1966).PubMedCrossRefGoogle Scholar
  48. 48.
    A. Nowotny, U. H. Behling, and H. L. Chang, Relation of structure to function in bacterial endotoxins. VIII. Biological activities in a polysaccharide-rich fraction, J. Immunol. 115: 199 (1975).PubMedGoogle Scholar
  49. 49.
    M. Ohta, M. Mori, T. Hasegawa, F. Hagase, I. Nakashima, S. Naito, and N. Kato, Further studies of the polysaccharide of Klebsiella pneumoniae possessing strong adjuvanticity. I. Production of the adjuvant polysaccharide by non-capsulated mutant, Microbiol. Immunol. 25: 939 (1981).PubMedGoogle Scholar
  50. 50.
    M. Ohta, J. Rothmann, E. Kovats, P. H. Pham, and A. Nowotny, Biological activities of lipopolysaccharides fractionated by preparative acrylamide gel electrophoresis, Microbiol. Immunol. 29: 1 (1985).PubMedGoogle Scholar
  51. 51.
    C.R.H. Raetz, S. Purcell, and K. Takayama, Molecular requirements for B-lymphocyte activation by Escherichia coli lipopolysaccharide, Proc. Natl. Acad. Sci. USA 80: 4624 (1983).PubMedCrossRefGoogle Scholar
  52. 52.
    D. Raichvarg, C. Brossard, and J. Agneray, Preparation of a nontoxic and immunogenic polysaccharide fraction from a Haemophilus influenza phenol-water extract, Infec. and Immun. 1: 171 (1980a).Google Scholar
  53. 53.
    D. Raichvarg, M. Guenounou, C. Brossard, J. E. Alouf, and J. Agneray, Endotoxin-like substances in bacterial cell-outer membrane: correlation between structure and biological activities of Haemophilus influenzae type A endotoxin, in: “Bacterial Endotoxins and Host Response,” M. K. Agarwal, ed., Elsevier/North-Holland Biomedical Press (1980b).Google Scholar
  54. 54.
    B. L. Ray, G. Painter, and C.R.H. Raetz, The biosynthesis of gram negative endotoxin. Formation of lipid A disaccharides from monosaccharide precursors in extracts of Escherichia coli, J. Biol. Chem. 259: 4852 (1984).Google Scholar
  55. 55.
    E. Ribi, R. Parker, S. M. Strain, Y. Mizuno, A. Nowotny, K. von Eschen, J. L. Cantrell, C. A. McLaughlin, K. M. Hwang, and M. B. Goren, Peptides as requirement for immunotherapy of the guinea-pig line-10 tumor with endotoxin, Cancer Immunol. Immunother. 7: 43 (1979).CrossRefGoogle Scholar
  56. 56.
    E. Ribi, K. Amano, J. Cantrell, S. Shwartzman, R. Parker, and K. Takayama, Preparation and antitumor activity of non-toxic lipid A, Cancer Immunol. Immunother. 12: 91 (1982).CrossRefGoogle Scholar
  57. 57.
    E. Ribi, J. L. Cantrell, K. Takayama, K. Amano, Enhancement of anti-tumor resistance by mycobacterial products and endotoxin, in: “Beneficial Effects of Endotoxins,” A. Nowotny, ed., Plenum Press, New York and London (1983).Google Scholar
  58. 58.
    E. T. Rietschel, S. Hase, M.-T. King, J. Redmond, and V. Lehmann, Chemical structure of lipid A, in: “Microbiology 1977,” D. Schiessinger, ed., American Society of Microbiology, Washington, D.C. (1977).Google Scholar
  59. 59.
    N. Rote, The role of long chain carboxylic acid in endotoxin, Ph.D. Thesis, Temple University, Philadelphia, Pennsylvania (1974).Google Scholar
  60. 60.
    J. Rothman, A. G. Johnson, H. Friedman, E. Kovats, P. H. Pham, F. Sanavi, A. M. Nowotny and A. Nowotny, Biological effects of White-type polysacharides of gram negative bacteria, J. Biol. Res. Mod. 4: 169 (1985).Google Scholar
  61. 61.
    J. A. Rudbach, R. L. Anacker, W. T. Haskins, K. C. Milner, and E. Ribi, Physical structure of a native protoplasmic polysaccharide from Escherichia coli, J. Immunol. 98: 1 (1967).PubMedGoogle Scholar
  62. 62.
    J. Samu, E. Kovats, T. Keler, and A. Nowotny, TLC and high-voltage TLC of endotoxins and their derivatives, Abstract, Fifth American-Eastern European Symposium on Liquid Chromatography, Hungarian Chemical Society, Budapest, Hungary (1985).Google Scholar
  63. 63.
    G. Shwartzman, Studies on Bacillus typhosus toxic substance. I. The phenomenon of local reactivity to B. Typhosus culture filtrate, J. Exp. Med. 48: 247 (1928).PubMedCrossRefGoogle Scholar
  64. 64.
    B. M. Sultzer, Chemical modification of endotoxin and inactivation of its biological properties, in: “Microbial Toxins,” Vol. 5, Kadis et al., eds., Academic Press, New York (1971).Google Scholar
  65. 65.
    B. M. Sultzer and G. W. Goodman, Endotoxin protein: A B-cell mitogen and polyclonal activator of C3H/HeJ lymphocytes, J. Exp. Med. 144: 821 (1976).PubMedCrossRefGoogle Scholar
  66. 66.
    K. Takayama, E. Ribi, and J. L. Cantrell, Isolation of a nontoxic Lipid A fraction containing tumor regression activity, Cancer Res. 41: 821 (1981).Google Scholar
  67. 67.
    D. Tripodi, Active sites of Serratia marcescens endotoxin preparations, Ph.D. Thesis, Temple University, Philadelphia, Pennsylvanyia (1965).Google Scholar
  68. 68.
    D. Tripodi and A. Nowotny, Relation of structure to function in bacterial O-antigens. V. Nature of active sites in endotoxic lipopolysaccharides of Serratia marcescens, Ann. N.Y. Acad. Sci. 133: 604 (1966).PubMedCrossRefGoogle Scholar
  69. 69.
    C. M. Tsai and C. E. Frash, A sensitive silver stain for detecting lipopolysaccharide in Polyacrylamide gels, Anal. Biochem. 119: 115 (1982).PubMedCrossRefGoogle Scholar
  70. 70.
    R. Urbaschek, Effects of bacterial products in granulopoiesis, Adv. Exp. Med. Biol. 121B-. 51 (1980).Google Scholar
  71. 71.
    O. Westphal and O. Luderitz, Chemische Erforschung von Lipopolysac- chariden gram negativer Bakterien, Angew. Chem. 66: 407 (1954).CrossRefGoogle Scholar
  72. 72.
    O. Westphal, A. Nowotny, O. Luderitz, H. Hurni, E. Eichenberger, and G. Schonholzer, The significance of the lipid component (lipid A) in the biological activities of bacterial endotoxins (lipopolysaccharides), Pharmeceutica. Acta. Helvetica (Germany) 33: 401 (1958).Google Scholar
  73. 73.
    O. Westphal, O. Luderitz, E. T. Rietschel, and C. Galanos, Bacterial lipopolysaccharide and its lipid A component: some historical and some current aspects, Biochem. Soc. Trans. 9: 191 (1980).Google Scholar
  74. 74.
    P. B. White, Notes on intestinal bacilli with special reference to smooth and rough races, J. Path, and. Bact 32: 85 (1929).CrossRefGoogle Scholar
  75. 75.
    P. D. Wightman and C.R.H. Wightman, The activation of protein kinase C by biologically active lipid moieties of lipopolysaccharide, J. Biol. Chem 259: 10048 (1984).PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Alois Nowotny
    • 1
  1. 1.Center for Oral Health ResearchUniversity of PennsylvaniaPhiladelphiaUSA

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