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.
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- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- NORINS L. C., HOLMES M. C. ANTINUCLEAR FACTOR IN MICE. J Immunol. 1964 Jul;93:148–154. [PubMed] [Google Scholar]
- 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]
- 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]
- Rudbach J. A. Molecular immunogenicity of bacterial lipopolysaccharide antigens: establishing a quantitative system. J Immunol. 1971 Apr;106(4):993–1001. [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]