Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1978 Aug 1;148(2):557–568. doi: 10.1084/jem.148.2.557

Macrophage stimulation by bacterial lipopolysaccharides. II. Evidence for differentiation signals delivered by lipid A and by a protein rich fraction of lipopolysaccharides

PMCID: PMC2184939  PMID: 359747

Abstract

Stimulation of macrophages to lyse tumor cells is a property common to lipopolysaccharide (LPS) extracted from a variety of smooth and rough bacterial strains by several different preparative procedures. The relationship between macrophage stimulation and the structural characteristics of LPS is defined. In protein-free LPS, lipid A bears the stimulatory signal which results in the differentiation of elicited macrophages into killer cells. The polysaccharide moiety is neither stimulatory itself nor does it block the activity of complete LPS on macrophages. Extraction of LPS by the butanol or Boivin procedures produces preparations in which LPS is complexed through its lipid A moiety to a protein rich component, LAP. Isolated LAP delivers a macrophage differentiation signal which is independent of lipid A. The presence of these two structurally distinct constituents in the cell walls of gram-negative bacteria broadens the biological environments in which they can stimulate macrophages in vivo.

Full Text

The Full Text of this article is available as a PDF (963.2 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ANACKER R. L., FINKELSTEIN R. A., HASKINS W. T., LANDY M., MILNER K. C., RIBI E., STASHAK P. W. ORIGIN AND PROPERTIES OF NATURALLY OCCURRING HAPTEN FROM ESCHERICHIA COLI. J Bacteriol. 1964 Dec;88:1705–1720. doi: 10.1128/jb.88.6.1705-1720.1964. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alexander P., Evans R. Endotoxin and double stranded RNA render macrophages cytotoxic. Nat New Biol. 1971 Jul 21;232(29):76–78. doi: 10.1038/newbio232076a0. [DOI] [PubMed] [Google Scholar]
  3. Anacker R. L., Bickel W. D., Haskins W. T., Milner K. C., Ribi E., Rudbach J. A. Frequency of occurrence of native hapten among enterobacterial species. J Bacteriol. 1966 Apr;91(4):1427–1433. doi: 10.1128/jb.91.4.1427-1433.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Andersson J., Möller G., Sjöberg O. Selective induction of DNA synthesis in T and B lymphocytes. Cell Immunol. 1972 Aug;4(4):381–393. doi: 10.1016/0008-8749(72)90040-8. [DOI] [PubMed] [Google Scholar]
  5. Betz S. J., Morrison D. C. Chemical and biologic properties of a protein-rich fraction of bacterial lipopolysaccharides. I. The in vitro murine lymphocyte response. J Immunol. 1977 Oct;119(4):1475–1481. [PubMed] [Google Scholar]
  6. Braun V. Molecular organization of the rigid layer and the cell wall of Escherichia coli. J Infect Dis. 1973 Jul;128(Suppl):9–16. doi: 10.1093/infdis/128.supplement_1.s9. [DOI] [PubMed] [Google Scholar]
  7. Currie G. A., Basham C. Activated macrophages release a factor which lyses malignant cells but not normal cells. J Exp Med. 1975 Dec 1;142(6):1600–1605. doi: 10.1084/jem.142.6.1600. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Doe W. F., Henson P. M. Macrophage stimulation by bacterial lipopolysaccharides. I. Cytolytic effect on tumor target cells. J Exp Med. 1978 Aug 1;148(2):544–556. doi: 10.1084/jem.148.2.544. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Evans R. Macrophages and the tumour bearing host. Br J Cancer Suppl. 1973 Aug;1:19–25. [PMC free article] [PubMed] [Google Scholar]
  10. Galanos C., Lüderitz O., Westphal O. A new method for the extraction of R lipopolysaccharides. Eur J Biochem. 1969 Jun;9(2):245–249. doi: 10.1111/j.1432-1033.1969.tb00601.x. [DOI] [PubMed] [Google Scholar]
  11. Galanos C., Lüderitz O., Westphal O. Preparation and properties of antisera against the lipid-A component of bacterial lipopolysaccharides. Eur J Biochem. 1971 Dec 22;24(1):116–122. doi: 10.1111/j.1432-1033.1971.tb19661.x. [DOI] [PubMed] [Google Scholar]
  12. Galanos C., Rietschel E. T., Lüderitz O., Westphal O. Interaction of lipopolysaccharides and lipid A with complement. Eur J Biochem. 1971 Mar 1;19(1):143–152. doi: 10.1111/j.1432-1033.1971.tb01298.x. [DOI] [PubMed] [Google Scholar]
  13. Gery I., Krüger J., Spiesel S. Z. Stimulation of B-lymphocytes by endotoxin. Reactions of thymus-deprived mice and karyotypic analysis of dividing cells in mice bearing T 6 T 6 thymus grafts. J Immunol. 1972 Apr;108(4):1088–1091. [PubMed] [Google Scholar]
  14. Gewurz H., Shin H. S., Mergenhagen S. E. Interactions of the complement system with endotoxic lipopolysaccharide: consumption of each of the six terminal complement components. J Exp Med. 1968 Nov 1;128(5):1049–1057. doi: 10.1084/jem.128.5.1049. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Jacobs M. D., Morrison D. C. Dissociation between mitogenicity and immunogenicity of TNP-lipopolysaccharide, a T-independent antigen. J Exp Med. 1975 Jun 1;141(6):1453–1458. doi: 10.1084/jem.141.6.1453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Koenig S., Hoffmann M. K., Thomas L. Induction of phenotypic lymphocyte differentiation in LPS unresponsive mice by an LPS-induced serum factor and by lipid A-associated protein. J Immunol. 1977 May;118(5):1910–1911. [PubMed] [Google Scholar]
  17. Loos M., Bitter-Suermann D., Dierich M. Interaction of the first (C1), the second (C2) and the fourth (C4) component of complement with different preparations of bacterial lipopolysaccharides and with lipid A. J Immunol. 1974 Mar;112(3):935–940. [PubMed] [Google Scholar]
  18. McIntire F. C., Sievert H. W., Barlow G. H., Finley R. A., Lee A. Y. Chemical, physical, biological properties of a lipopolysaccharide from Escherichia coli K-235. Biochemistry. 1967 Aug;6(8):2363–2372. doi: 10.1021/bi00860a011. [DOI] [PubMed] [Google Scholar]
  19. Morrison D. C., Betz S. J., Jacobs D. M. Isolation of a lipid A bound polypeptide responsible for "LPS-initiated" mitogenesis of C3H/HeJ spleen cells. J Exp Med. 1976 Sep 1;144(3):840–846. doi: 10.1084/jem.144.3.840. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Morrison D. C., Cochrane C. G. Direct evidence for Hageman factor (factor XII) activation by bacterial lipopolysaccharides (endotoxins). J Exp Med. 1974 Sep 1;140(3):797–811. doi: 10.1084/jem.140.3.797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Morrison D. C., Jacobs D. M. Binding of polymyxin B to the lipid A portion of bacterial lipopolysaccharides. Immunochemistry. 1976 Oct;13(10):813–818. doi: 10.1016/0019-2791(76)90181-6. [DOI] [PubMed] [Google Scholar]
  22. Morrison D. C., Jacobs D. M. Inhibition of lipopolysaccharide-initiated activation of serum complement by polymyxin B. Infect Immun. 1976 Jan;13(1):298–301. doi: 10.1128/iai.13.1.298-301.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Morrison D. C., Kline L. F. Activation of the classical and properdin pathways of complement by bacterial lipopolysaccharides (LPS). J Immunol. 1977 Jan;118(1):362–368. [PubMed] [Google Scholar]
  24. Morrison D. C., Leive L. Fractions of lipopolysaccharide from Escherichia coli O111:B4 prepared by two extraction procedures. J Biol Chem. 1975 Apr 25;250(8):2911–2919. [PubMed] [Google Scholar]
  25. Niwa M., Milner K. C., Ribi E., Rudbach J. A. Alteration of physical, chemical, and biological properties of endotoxin by treatment with mild alkali. J Bacteriol. 1969 Mar;97(3):1069–1077. doi: 10.1128/jb.97.3.1069-1077.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Parr I., Wheeler E., Alexander P. Similarities of the anti-tumour actions of endotoxin, lipid A and double-stranded RNA. Br J Cancer. 1973 May;27(5):370–389. doi: 10.1038/bjc.1973.45. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sultzer B. M., Goodman G. W. Endotoxin protein: a B-cell mitogen and polyclonal activator of C3H/HeJ lymphocytes. J Exp Med. 1976 Sep 1;144(3):821–827. doi: 10.1084/jem.144.3.821. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Von Eschen K. B., Rudbach J. A. Immunological responses of mice to native protoplasmic polysaccharide and lipopolysaccharide: functional separation of the two signals required to stimulate a secondary antibody response. J Exp Med. 1974 Dec 1;140(6):1604–1614. doi: 10.1084/jem.140.6.1604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Watson J. Differentiation of B lymphocytes in C3H/HeJ mice: the induction of Ia antigens by lipopolysaccharide. J Immunol. 1977 Mar;118(3):1103–1108. [PubMed] [Google Scholar]
  30. Westphal O. Bacterial endotoxins. The second Carl Prausnitz Memorial Lecture. Int Arch Allergy Appl Immunol. 1975;49(1-2):1–43. [PubMed] [Google Scholar]
  31. Wober W., Alaupović P. Studies on the protein moiety of endotoxin from gram-negative bacteria. Characterization of the protein moiety isolated by phenol treatment of endotoxin from Serratia marcescens 08 and Escherichia coli 0 141:K85(B). Eur J Biochem. 1971 Apr;19(3):340–356. doi: 10.1111/j.1432-1033.1971.tb01323.x. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES