Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1974 Oct 31;140(5):1189–1206. doi: 10.1084/jem.140.5.1189

RELEASE OF DNA IN CIRCULATING BLOOD AND INDUCTION OF ANTI-DNA ANTIBODIES AFTER INJECTION OF BACTERIAL LIPOPOLYSACCHARIDES

Gilbert J Fournié 1, Paul H Lambert 1, Peter A Miescher 1
PMCID: PMC2139721  PMID: 4607609

Abstract

The present data demonstrate the induction of antisingle-stranded (SS) DNA and antidouble-stranded DNA antibodies in various strains of mice, including athymic C57BL/6 nude mice, after the injection of bacterial lipopolysaccharide (LPS). This anti-DNA response is dose dependent and varies quantitatively according to the strain of the injected mice. It is not correlated to the H-2 histocompatibility locus nor to the immune response to LPS. The lipid A fraction appears to be the active part of the LPS molecule for this particular effect. In addition, it was found that DNA is released in circulating blood a few hours after the injection of LPS. Most of the DNA released has physicochemical and immunochemical characteristics of SS DNA. Therefore, the anti-DNA response induced by injections of LPS may be the result of a release of DNA in a particularly immunogenic form at a time when the immune system, in particular the B lymphocytes, is rendered capable by LPS of developing an immune response to such a soluble antigen. These effects of LPS may account for the triggering or the exacerbation of ante-DNA antibodies during infections with gram-negative bacteria, and a similar mechanism may be involved in the pathogenesis of systemic lupus erythematosus.

Full Text

The Full Text of this article is available as a PDF (1.1 MB).

Selected References

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

  1. Allison A. C. Mechanisms of tolerance and autoimmunity. Ann Rheum Dis. 1973 Jul;32(4):283–293. doi: 10.1136/ard.32.4.283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Andersson J., Sjöberg O., Möller G. Induction of immunoglobulin and antibody synthesis in vitro by lipopolysaccharides. Eur J Immunol. 1972 Aug;2(4):349–353. doi: 10.1002/eji.1830020410. [DOI] [PubMed] [Google Scholar]
  3. Armerding D., Katz D. H. Activation of T and B lymphocytes in vitro. I. Regulatory influence of bacterial lipopolysaccharide (LPS) on specific T-cell helper function. J Exp Med. 1974 Jan 1;139(1):24–43. doi: 10.1084/jem.139.1.24. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Burnet F. M., Holmes M. C. The natural history of the NZB/NZW F1 hybrid mouse: a laboratory model of systemic lupus erythematosus. Australas Ann Med. 1965 Aug;14(3):185–191. doi: 10.1111/imj.1965.14.3.185. [DOI] [PubMed] [Google Scholar]
  5. CEPPELLINI R., POLLI E., CELADA F. A DNA-reacting factor in serum of a patient with lupus erythematosus diffusus. Proc Soc Exp Biol Med. 1957 Dec;96(3):572–574. doi: 10.3181/00379727-96-23544. [DOI] [PubMed] [Google Scholar]
  6. CHRISTIAN C. L., DESIMONE A. R., ABRUZZO J. L. ANTI-DNA ANTIBODIES IN HYPERIMMUNIZED RABBITS. J Exp Med. 1965 Feb 1;121:309–321. doi: 10.1084/jem.121.2.309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chiller J. M., Skidmore B. J., Morrison D. C., Weigle W. O. Relationship of the structure of bacterial lipopolysaccharides to its function in mitogenesis and adjuvanticity. Proc Natl Acad Sci U S A. 1973 Jul;70(7):2129–2133. doi: 10.1073/pnas.70.7.2129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chiller J. M., Weigle W. O. Termination of tolerance to human gamma globulin in mice by antigen and bacterial lipopolysaccharide (endotoxin). J Exp Med. 1973 Mar 1;137(3):740–750. doi: 10.1084/jem.137.3.740. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chused T. M., Steinberg A. D., Talal N. The clearance and localization of nucleic acids by New Zealand and normal mice. Clin Exp Immunol. 1972 Dec;12(4):465–476. [PMC free article] [PubMed] [Google Scholar]
  10. Commerford S. L. Iodination of nucleic acids in vitro. Biochemistry. 1971 May 25;10(11):1993–2000. doi: 10.1021/bi00787a005. [DOI] [PubMed] [Google Scholar]
  11. East J., de Sousa M. A., Parrott D. M. Immunopathology of New Zealand black (NZB) mice. Transplantation. 1965 Nov;3(6):711–729. doi: 10.1097/00007890-196511000-00003. [DOI] [PubMed] [Google Scholar]
  12. FINE J., FRANK E. D., RAVIN H. A., RUTENBERG S. H., SCHWEINBURG F. B. The bacterial factor in traumatic shock. N Engl J Med. 1959 Jan 29;260(5):214–220. doi: 10.1056/NEJM195901292600505. [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. HEILMAN D. H., BERNTON H. W. The effect of endotoxin on tissue cultures of spleen of normal and tuberculin-sensitive animals. Am Rev Respir Dis. 1961 Dec;84:862–871. doi: 10.1164/arrd.1961.84.6.862. [DOI] [PubMed] [Google Scholar]
  15. HOLMAN H. R., KUNKEL H. G. Affinity between the lupus erythematosus serum factor and cell nuclei and nucleoprotein. Science. 1957 Jul 26;126(3265):162–163. doi: 10.1126/science.126.3265.162. [DOI] [PubMed] [Google Scholar]
  16. Howie J. B., Helyer B. J. The immunology and pathology of NZB mice. Adv Immunol. 1968;9:215–266. doi: 10.1016/s0065-2776(08)60444-7. [DOI] [PubMed] [Google Scholar]
  17. Hughes G. R. Significance of anti-D.N.A. antibodies in systemic lupus erythematosus. Lancet. 1971 Oct 16;2(7729):861–863. doi: 10.1016/s0140-6736(71)90234-0. [DOI] [PubMed] [Google Scholar]
  18. JOHNSON A. G., GAINES S., LANDY M. Studies on the O antigen of Salmonella typhosa. V. Enhancement of antibody response to protein antigens by the purified lipopolysaccharide. J Exp Med. 1956 Feb 1;103(2):225–246. doi: 10.1084/jem.103.2.225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kagnoff M. F., Billings P., Cohn M. Functional characteristics of Peyer's patch lymphoid cells. II. Lipopolysaccharide is thymus dependent. J Exp Med. 1974 Feb 1;139(2):407–413. doi: 10.1084/jem.139.2.407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Koffler D., Agnello V., Thoburn R., Kunkel H. G. Systemic lupus erythematosus: prototype of immune complex nephritis in man. J Exp Med. 1971 Sep 1;134(3):169–179. [PMC free article] [PubMed] [Google Scholar]
  21. Lambert P. H., Dixon F. J. Genesis of antinuclear antibody in NZB-W mice: role of genetic factors and of viral infections. Clin Exp Immunol. 1970 Jun;6(6):829–839. [PMC free article] [PubMed] [Google Scholar]
  22. Lambert P. H., Dixon F. J. Pathogenesis of the glomerulonephritis of NZB/W mice. J Exp Med. 1968 Mar 1;127(3):507–522. doi: 10.1084/jem.127.3.507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lamelin J. P., Lisowska-Bernstein B., Matter A., Ryser J. E., Vassalli P. Mouse thymus-independent and thymus-derived lymphoid cells. I. Immunofluorescent and functional studies. J Exp Med. 1972 Nov 1;136(5):984–1007. doi: 10.1084/jem.136.5.984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Louis J. A., Chiller J. M., Weigle W. O. The ability of bacterial lipopolysaccharide to modulate the induction of unresponsiveness to a state of immunity. Cellular parameters. J Exp Med. 1973 Dec 1;138(6):1481–1495. doi: 10.1084/jem.138.6.1481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. MIESCHER P. The antigenic constituents of the neutrophilic leukocyte with special reference to the L. E. phenomenon. Vox Sang. 1957 Jul;2(3):145–158. doi: 10.1111/j.1423-0410.1957.tb03450.x. [DOI] [PubMed] [Google Scholar]
  26. Mellors R. C., Aoki T., Huebner R. J. Further implication of murine leukemia-like virs in the disorders of NZB mice. J Exp Med. 1969 May 1;129(5):1045–1062. doi: 10.1084/jem.129.5.1045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Möller G., Michael G. Frequency of antigen-sensitive cells to thymus-independent antigens. Cell Immunol. 1971 Aug;2(4):309–316. doi: 10.1016/0008-8749(71)90065-7. [DOI] [PubMed] [Google Scholar]
  28. NORINS L. C., HOLMES M. C. ANTINUCLEAR FACTOR IN MICE. J Immunol. 1964 Jul;93:148–154. [PubMed] [Google Scholar]
  29. ROSEN F. S. The endotoxins of gram-negative bacteria and host resistance. N Engl J Med. 1961 May 4;264:919–923. doi: 10.1056/NEJM196105042641807. [DOI] [PubMed] [Google Scholar]
  30. ROWLEY D. Rapidly induced changes in the level of non-specific immunity in laboratory animals. Br J Exp Pathol. 1956 Jun;37(3):223–234. [PMC free article] [PubMed] [Google Scholar]
  31. Rudbach J. A. Molecular immunogenicity of bacterial lipopolysaccharide antigens: establishing a quantitative system. J Immunol. 1971 Apr;106(4):993–1001. [PubMed] [Google Scholar]
  32. Steinberg A. D., Pincus T., Talal N. DNA-binding assay for detection of anti-DNA antibodies in NZB-NZW F1 mice. J Immunol. 1969 Mar;102(3):788–790. [PubMed] [Google Scholar]
  33. Stollar B. D., Fuchs S., Mozes E. Immune response of mice to nucleic acids: strain-dependent differences in magnitude and class of antibody production. J Immunol. 1973 Jul;111(1):121–129. [PubMed] [Google Scholar]
  34. Stollar B. D., Fuchs S., Mozes E. Immune response of mice to nucleic acids: strain-dependent differences in magnitude and class of antibody production. J Immunol. 1973 Jul;111(1):121–129. [PubMed] [Google Scholar]
  35. Tan E. M., Natali P. G. Comparative study of antibodies to native and denatured DNA. J Immunol. 1970 Apr;104(4):902–906. [PubMed] [Google Scholar]
  36. Tonietti G., Oldstone M. B., Dixon F. J. The effect of induced chronic viral infections on the immunologic diseases of New Zealand mice. J Exp Med. 1970 Jul 1;132(1):89–109. doi: 10.1084/jem.132.1.89. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Weigle W. O. Recent observations and concepts in immunological unresponsiveness and autoimmunity. Clin Exp Immunol. 1971 Oct;9(4):437–447. [PMC free article] [PubMed] [Google Scholar]
  38. Wold R. T., Young F. E., Tan E. M., Farr R. S. Deoxyribonucleic acid antibody: a method to detect its primary interaction with deoxyribonucleic acid. Science. 1968 Aug 23;161(3843):806–807. doi: 10.1126/science.161.3843.806. [DOI] [PubMed] [Google Scholar]

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

RESOURCES