Regulation of Lipopolysaccharide Biologic Activity by Polysaccharide

  • D. C. Morrison
  • S. W. Vukajlovich
  • S. A. Goodman
  • H.-W. Wollenweber
Conference paper
Part of the Bayer-Symposium book series (BAYER-SYMP, volume 8)


Bacterial lipopolysaccharides (LPS) have been implicated as a major contributing factor in the pathogenesis of gram-negative bacterial infections. Biochemical investigations have defined in detail the chemical structure of both the polysaccharide and the lipid A components. In this respect, there is now overwhelming evidence to suggest that the presence of lipid A is essential for the expression of most the multiple pathophysiologic and immunoregulatory properties of LPS. There is, in contrast, significantly less information on the role of the polysaccharide in regulating the biologic expression of the active lipid A component present in native LPS preparations. We have, therefore, performed experiments to examine this question by creating LPS macromolecules which vary significantly in their relative content of lipid A and polysaccharide. One protocol has employed the generation of LPS macromolecular hybrids in which lipid A-rich LPS molecules have been incorporated into native polysaccharide-containing LPS preparations. A second procedure has employed molecular sieve chromatography of detergent-dissociated LPS to generate LPS macromolecules with reduced subunit heterogeneity. The results of these combined studies indicate that the presence of polysaccharide can negatively regulate lipid A activity by two distinct mechanisms. They further support the concept that polysaccharide composition may be as critical a factor in the manifestation of LPS endotoxin activity as is the actual content of lipid A.


Bacterial Endotoxin Immunostimulatory Activity Murine Splenocytes Molecular Sieve Chromatography Macromolecular Aggregate 
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.


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  1. 1.
    Pfeiffer R (1892) Untersuchungen über das Choleragift. Z Hyg Infektionskran 11: 393–412CrossRefGoogle Scholar
  2. 2.
    Boivin A, Mesrobeanu L (1935) Recherches sur les antigenes somatiques et sur les endotoxines des bacteries: I. Considerations generales et expose des Techniques utilisees. Rev Immunol (Paris) 1: 553–569Google Scholar
  3. 3.
    Westphal O (1975) Bacterial endotoxins. Int Arch Allergy Appl Immunol 49: 1–43PubMedCrossRefGoogle Scholar
  4. 4.
    Ziegler EJ, McCutchen JA, Fierer J, Glauser MP, Sadoff JC, Douglas H, Braude AI (1982) N Engl J Med 307: 1225–1230PubMedCrossRefGoogle Scholar
  5. 5.
    Goebel WF, Binkley F, Perlman E (1945) Studies on the Flexner group of dysentery Bacilli: I. The specific antigens of S. paradysenteriae. J Med 81: 315–330Google Scholar
  6. 6.
    Westphal O, Luderitz O, Bister F (1952) Über die Extraktion von Bakterien mit Phenol-Wasser. Z Naturforsch 7B: 148–155Google Scholar
  7. 7.
    Luderitz O, Freundenberg MA, Galanos C, Lehmann V, Rietschel ET, Shaw DW (1982) In: Razin S, Rottem S (eds) Microbial membrane lipids. Academic, New York, pp 79–151Google Scholar
  8. 8.
    Rietschel ET, Galanos C, Luderitz O, Westphal O (1982) In: Webb DR (ed) Immunopharmacology and the regulation of leukocyte function. Dekker, New York, pp 183–229Google Scholar
  9. 9.
    Morrison DC, Alving CA (eds) (1984) Symposium Molecular Concepts of Lipid A. Rev Infect Dis 4: 427–587Google Scholar
  10. 10.
    Rick PD, Osborn MJ (1977) Lipid A mutants of Salmonella typhimurium. Characterization of a conditional lethal mutant in 3-deoxy-D-mannooctulosonate-8-phosphate synthetase. J Biol Chem 252: 4895–4903PubMedGoogle Scholar
  11. 11.
    Hitchcock PJ, Morrison DC (1984) The protein component of bacterial endotoxins. In: Rietschel ET (ed) Chemistry of endotoxin. Elsevier North Holland, AmsterdamGoogle Scholar
  12. 12.
    Morrison DC, Oades ZG, Betz SJ (1980) The role of lipid A and lipid A- associated protein in cell degranulation mechanisms. In: Eaker D, Wadstrom T (eds) Natural toxins. Pergammon, New York, pp 287–294Google Scholar
  13. 13.
    Sultzer BM, Goodman GW, Eisenstein TK (1980) Endotoxin protein as an immunostimulant. In: Schlessinger D (ed) Microbiology-80. American Society for Microbiology, Washington, pp 61–65Google Scholar
  14. 14.
    Goldman RC, White C, Leive L (1981) Identification of outer membrane proteins, including known lymphocyte mitogens as the endotoxin protein of E. coli Olli. J Immunol 127: 1290–1294Google Scholar
  15. 15.
    Morrison DC, Ulevitch RJ (1978) A review — The interaction of bacterial endotoxins with cellular and humoral mediation systems. Am J Pathol 93: 527–618Google Scholar
  16. 16.
    Tanamoto K-I, Zahringer U, McKenzie GR, Galanos C, Rietschel ET, Luderitz O, Kusumoto S, Shiba T (1984) Biological activities of synthetic lipid A analogs: Pyrogenicity, lethal toxicity, anticomplement activity, and induction of gelation of Limulus amoebocyte lysate. Infect Immun 44: 421–426PubMedGoogle Scholar
  17. 17.
    Palva ET, Makela PH (1980) Lipopolysaccharide heterogeneity in Salmonella typhimurium analyzed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. Eur J Biochem 107: 137PubMedCrossRefGoogle Scholar
  18. 18.
    Goldman RC, Leive L (1980) Heterogeneity of antigenic-side-chain length in lipopolysaccharide from Escherichia coli 0111 and Salmonella typhimurium LT2. Eur J Biochem 107: 145PubMedCrossRefGoogle Scholar
  19. 19.
    Rudbach JA, Milner KC, Ribi E (1967) Hybrid formation between bacterial endotoxins. J Exp Med 126: 62–79CrossRefGoogle Scholar
  20. 20.
    Westphal O, Lüderitz O, Bister F (1952) Über die Extraktion von Bakterien mit Phenol-Wasser. Z Naturforsch [c] 7B: 148–155Google Scholar
  21. 21.
    Galanos C, Luderitz O, Westphal O (1969) A new method for the extraction of R lipopolysaccharides. Eur J Biochem 9: 945CrossRefGoogle Scholar
  22. 22.
    Ulevitch RJ (1978) The preparation and characterization of a radioiodinated bacterial lipopolysaccharide. Immunochemistry 15: 164CrossRefGoogle Scholar
  23. 23.
    Vukajlovich SW, Morrison DC (1983) Conversion of lipopolysaccharides to molecular aggregates with reduced subunit heterogeneity: demonstration of LPS-responsiveness in “endotoxin-unresponsive” C3H/HeJ splenocytes. J Immunol 130: 2804–2808PubMedGoogle Scholar
  24. 24.
    Goodman SA, Morrison DC (1984) Selective association of lipid rich R-like lipopolysaccharide (LPS) subunits with murine spleen cells. Mol Immunol 21: 689–697PubMedCrossRefGoogle Scholar
  25. 25.
    Morrison DC, Oades ZG, Vukajlovich SJ, Goodman SA, Duncan RL (1984) Mechanism of action of endotoxin at the cellular level. In: Keppler D (ed) Mechanisms of hepatocyte injury and death. MTP, LancasterGoogle Scholar
  26. 26.
    Carr C, Morrison DC (1984) Lipopolysaccharide interaction with rabbit erythrocyte membranes. Infect Immun 43: 600–606PubMedGoogle Scholar
  27. 27.
    Haeffner-Cavaillon N, Chaby R, Cavaillon JM, Szabo L (1982) Lipopolysaccharide receptor on rabbit peritoneal macrophages: I. Binding characteristics. J Immunol 128: 1950–1954PubMedGoogle Scholar
  28. 28.
    Morrison DC, Kline LF (1977) Activation of the classical and properdin pathways of complement by bacterial lipopolysaccharides. J Immunol 118: 362–368PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1985

Authors and Affiliations

  • D. C. Morrison
  • S. W. Vukajlovich
  • S. A. Goodman
  • H.-W. Wollenweber

There are no affiliations available

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