Skip to main content
NCBI home page
Immunology logoLink to Immunology
. 1988 Mar;63(3):471–475.

Immunosuppressive and anti-proliferative effects of a macrotetrolide antibiotic, tetranactin.

Y Tanouchi 1, H Shichi 1
PMCID: PMC1454748  PMID: 3258281

Abstract

The macrotetrolide tetranactin suppressed the appearance of experimental autoimmune uveoretinitis induced in Lewis rats with a soluble retinal antigen (S-antigen). The drug at 1 ng/ml inhibited the mitogen activation of unfractionated lymphocytes; incorporation of radiolabelled precursors such as thymidine, uridine and leucine into the cells was markedly reduced. The synthesis and release of IL-2 by mitogen-activated lymphocytes was significantly suppressed in the presence of tetranactin. Incorporation of 45Ca was also inhibited, while intracellular Na+ levels were increased. In view of the ionophore property of tetranactin, it was suggested that the drug might demonstrate its immunosuppressive effect by affecting intracellular cation concentrations.

Full text

PDF
471

Selected References

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

  1. Ando K., Oishi H., Hirano S., Okutomi T., Suzuki K. Tetranactin, a new miticidal antibiotic. I. Isolation, characterization and properties of tetranactin. J Antibiot (Tokyo) 1971 Jun;24(6):347–352. doi: 10.7164/antibiotics.24.347. [DOI] [PubMed] [Google Scholar]
  2. Birx D. L., Berger M., Fleisher T. A. The interference of T cell activation by calcium channel blocking agents. J Immunol. 1984 Dec;133(6):2904–2909. [PubMed] [Google Scholar]
  3. Borel J. F. Comparative study of in vitro and in vivo drug effects on cell-mediated cytotoxicity. Immunology. 1976 Oct;31(4):631–641. [PMC free article] [PubMed] [Google Scholar]
  4. Bunjes D., Hardt C., Röllinghoff M., Wagner H. Cyclosporin A mediates immunosuppression of primary cytotoxic T cell responses by impairing the release of interleukin 1 and interleukin 2. Eur J Immunol. 1981 Aug;11(8):657–661. doi: 10.1002/eji.1830110812. [DOI] [PubMed] [Google Scholar]
  5. Colombani P. M., Robb A., Hess A. D. Cyclosporin A binding to calmodulin: a possible site of action on T lymphocytes. Science. 1985 Apr 19;228(4697):337–339. doi: 10.1126/science.3885394. [DOI] [PubMed] [Google Scholar]
  6. Das N. D., Ulshafer R. J., Zam Z. S., Leverenz V. R., Shichi H. Radioimmunocytochemical localization of retinal S-antigen with monoclonal antibodies. J Histochem Cytochem. 1984 Aug;32(8):834–838. doi: 10.1177/32.8.6379036. [DOI] [PubMed] [Google Scholar]
  7. Gillis S., Ferm M. M., Ou W., Smith K. A. T cell growth factor: parameters of production and a quantitative microassay for activity. J Immunol. 1978 Jun;120(6):2027–2032. [PubMed] [Google Scholar]
  8. Graven S. N., Lardy H. A., Johnson D., Rutter A. Antibiotics as tools for metabolic studies. V. Effect of nonactin, monactin, dinactin, and trinactin on oxidative phosphorylation and adenosine triphosphatase induction. Biochemistry. 1966 May;5(5):1729–1735. doi: 10.1021/bi00869a040. [DOI] [PubMed] [Google Scholar]
  9. Hess A. D., Colombani P. M., Esa A. H. Cyclosporine and the immune response: basic aspects. Crit Rev Immunol. 1986;6(2):123–149. [PubMed] [Google Scholar]
  10. Jung K., Pergande M. Influence of cyclosporin A on the respiration of isolated rat kidney mitochondria. FEBS Lett. 1985 Apr 8;183(1):167–169. doi: 10.1016/0014-5793(85)80977-7. [DOI] [PubMed] [Google Scholar]
  11. LeGrue S. J., Friedman A. W., Kahan B. D. Binding of cyclosporine by human lymphocytes and phospholipid vesicles. J Immunol. 1983 Aug;131(2):712–718. [PubMed] [Google Scholar]
  12. LeGrue S. J., Munn C. G. Comparison of the immunosuppressive effects of cyclosporine, lipid-soluble anesthetics, and calmodulin antagonists. Response to exogenous interleukin 2. Transplantation. 1986 Dec;42(6):679–685. doi: 10.1097/00007890-198612000-00019. [DOI] [PubMed] [Google Scholar]
  13. MacDonald H. R., Nabholz M. T-cell activation. Annu Rev Cell Biol. 1986;2:231–253. doi: 10.1146/annurev.cb.02.110186.001311. [DOI] [PubMed] [Google Scholar]
  14. Metcalfe S. M., Watson J. V., Kass T. Cyclosporin-A binds lymphocyte surface receptors induced by activation. Immunol Lett. 1985;10(3-4):151–157. doi: 10.1016/0165-2478(85)90070-7. [DOI] [PubMed] [Google Scholar]
  15. Nordmann J. P., De Kozak Y., Le Hoang P., Faure J. P. Cyclosporine therapy of guinea-pig autoimmune uveoretinitis induced with autologous retina. J Ocul Pharmacol. 1986 Fall;2(4):325–333. doi: 10.1089/jop.1986.2.325. [DOI] [PubMed] [Google Scholar]
  16. Nussenblatt R. B., Kuwabara T., de Monasterio F. M., Wacker W. B. S-antigen uveitis in primates. A new model for human disease. Arch Ophthalmol. 1981 Jun;99(6):1090–1092. doi: 10.1001/archopht.1981.03930011090021. [DOI] [PubMed] [Google Scholar]
  17. Nussenblatt R. B., Rodrigues M. M., Wacker W. B., Cevario S. J., Salinas-Carmona M. C., Gery I. Cyclosporin a. Inhibition of experimental autoimmune uveitis in Lewis rats. J Clin Invest. 1981 Apr;67(4):1228–1231. doi: 10.1172/JCI110138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Rosoff P. M., Terres G. Cyclosporine A inhibits Ca2+-dependent stimulation of the Na+/H+ antiport in human T cells. J Cell Biol. 1986 Aug;103(2):457–463. doi: 10.1083/jcb.103.2.457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Segel G. B., Hollander M. M., Gordon B. R., Klemperer M. R., Lichtman M. A. A rapid phytohemagglutinin induced alteration in lymphocyte potassium permeability. J Cell Physiol. 1975 Oct;86(2 Pt 2 Suppl 1):327–335. doi: 10.1002/jcp.1040860404. [DOI] [PubMed] [Google Scholar]
  20. Shinohara T., Piatigorsky J. Anion and cation effects on delta-crystallin synthesis in the cultured embryonic chick lens and in a reticulocyte lysate. Exp Eye Res. 1980 Apr;30(4):351–360. doi: 10.1016/0014-4835(80)90050-0. [DOI] [PubMed] [Google Scholar]
  21. Shinohara T., Piatigorsky J. Regulation of protein synthesis, intracellular electrolytes and cataract formation in vitro. Nature. 1977 Dec 1;270(5636):406–411. doi: 10.1038/270406a0. [DOI] [PubMed] [Google Scholar]
  22. Suzuki K., Nawata Y., Ando K. Tetranactin, a new miticidal antibiotic. V. Quantitative determination macrotetrolide antibiotics. J Antibiot (Tokyo) 1971 Oct;24(10):675–679. doi: 10.7164/antibiotics.24.675. [DOI] [PubMed] [Google Scholar]
  23. Tanouchi Y., Shichi H. Immunosuppressive effects of polynactins (tetranactin, trinactin and dinactin) on experimental autoimmune uveoretinitis in rats. Jpn J Ophthalmol. 1987;31(2):218–229. [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES