Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1982 Mar;79(6):1879–1883. doi: 10.1073/pnas.79.6.1879

Genetic analysis of the role of cAMP in mediating effects of interferon.

J Schneck, B Rager-Zisman, O M Rosen, B R Bloom
PMCID: PMC346084  PMID: 6177003

Abstract

The effects of interferon (IFN) on Fc receptor-mediated phagocytosis, intracellular cAMP levels, antiviral activity, and growth inhibition were analyzed in a cloned macrophage-like cell line, J774.2, and variants derived from it. Purified IFN increased Fc receptor-mediated phagocytosis in J774.2 cells, and in cAMP-responsive nonphagocytic variants but was without effect in cAMP-unresponsive nonphagocytic variants, in adenylate cyclase-deficient variants, and in cAMP-dependent protein kinase-deficient variants. Under conditions in which IFN augmented phagocytosis, it increased intracellular levels of cAMP. Parental cells were highly sensitive to IFN-mediated growth inhibition. In contrast, cAMP-dependent protein kinase-deficient variants were only 1/100th as sensitive to growth inhibition by IFN. All cell lines tested, both responsive and unresponsive to cAMP, were equally protected by IFN against infection with vesicular stomatitis virus, demonstrating that the antiviral state was independent of cAMP. These results indicate that, in transformed macrophages, stimulation of phagocytosis and inhibition of growth by IFN are mediated through intracellular cAMP, whereas the antiviral state induced by IFN is independent of cAMP.

Full text

PDF
1879

Selected References

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

  1. Brouty-Boyé D., Tovey M. G. Inhibition by interferon of thymidine uptake in chemostat cultures of L1210 cells. Intervirology. 1978;9(4):243–252. doi: 10.1159/000148942. [DOI] [PubMed] [Google Scholar]
  2. Diamond B., Scharff M. D. IgG1 and IgG2b share the Fc receptor on mouse macrophages. J Immunol. 1980 Aug;125(2):631–633. [PubMed] [Google Scholar]
  3. Diamond B., Yelton D. E. A new Fc receptor on mouse macrophages binding IgG3. J Exp Med. 1981 Mar 1;153(3):514–519. doi: 10.1084/jem.153.3.514. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Donahoe R. M., Huang K. Y. Interferon preparations enhance phagocytosis in vivo. Infect Immun. 1976 Apr;13(4):1250–1257. doi: 10.1128/iai.13.4.1250-1257.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Farrell P. J., Sen G. C., Dubois M. F., Ratner L., Slattery E., Lengyel P. Interferon action: two distinct pathways for inhibition of protein synthesis by double-stranded RNA. Proc Natl Acad Sci U S A. 1978 Dec;75(12):5893–5897. doi: 10.1073/pnas.75.12.5893. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Friedman R. M., Pastan I. Interferon and cyclic-3'5'-adenosine monophosphate: potentiation of antiviral activity. Biochem Biophys Res Commun. 1969 Aug 22;36(5):735–740. doi: 10.1016/0006-291x(69)90671-8. [DOI] [PubMed] [Google Scholar]
  7. Fuse A., Kuwata T. Inhibition of DNA synthesis and alteration of cyclic adenosine 3',5'-monophosphate levels in RSa cells by human leukocyte interferon. J Natl Cancer Inst. 1978 Jun;60(6):1227–1232. doi: 10.1093/jnci/60.6.1227. [DOI] [PubMed] [Google Scholar]
  8. Gresser I., Brouty-Boyé D., Thomas M. T., Macieira-Coelho A. Interferon and cell division. I. Inhibition of the multiplication of mouse leukemia L 1210 cells in vitro by interferon preparations. Proc Natl Acad Sci U S A. 1970 Aug;66(4):1052–1058. doi: 10.1073/pnas.66.4.1052. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gresser I., De Maeyer-Guignard J., Tovey M. G., De Maeyer E. Electrophoretically pure mouse interferon exerts multiple biologic effects. Proc Natl Acad Sci U S A. 1979 Oct;76(10):5308–5312. doi: 10.1073/pnas.76.10.5308. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hamburg S. I., Fleit H. B., Unkeless J. C., Rabinovitch M. Mononuclear phagocytes: responders to and producers of interferon. Ann N Y Acad Sci. 1980;350:72–90. doi: 10.1111/j.1749-6632.1980.tb20609.x. [DOI] [PubMed] [Google Scholar]
  11. Kerr I. M., Brown R. E. pppA2'p5'A2'p5'A: an inhibitor of protein synthesis synthesized with an enzyme fraction from interferon-treated cells. Proc Natl Acad Sci U S A. 1978 Jan;75(1):256–260. doi: 10.1073/pnas.75.1.256. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kimchi A., Shure H., Revel M. Regulation of lymphocyte mitogenesis by (2'--5') oligo-isoadenylate. Nature. 1979 Dec 20;282(5741):849–851. doi: 10.1038/282849a0. [DOI] [PubMed] [Google Scholar]
  13. Knight E., Jr Antiviral and cell growth inhibitory activities reside in the same glycoprotein of human fibroblast interferon. Nature. 1976 Jul 22;262(5566):302–303. doi: 10.1038/262302a0. [DOI] [PubMed] [Google Scholar]
  14. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  15. Muschel R. J., Rosen N., Bloom B. R. Isolation of variants in phagocytosis of a macrophage-like continuous cell line. J Exp Med. 1977 Jan 1;145(1):175–186. doi: 10.1084/jem.145.1.175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Muschel R. J., Rosen N., Rosen O. M., Bloom B. R. Modulation of Fc-mediated phagocytosis by cyclic AMP and insulin in a macrophage-like cell line. J Immunol. 1977 Nov;119(5):1813–1820. [PubMed] [Google Scholar]
  17. Nowakowski M., Feldman J. D., Kano S., Bloom B. R. The production of vesicular stomatitis virus by antigen- or mitogen-stimulated lymphocytes and continuous lymphoblastoid lines. J Exp Med. 1973 Apr 1;137(4):1042–1059. doi: 10.1084/jem.137.4.1042. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ralph P., Moore M. A., Nilsson K. Lysozyme synthesis by established human and murine histiocytic lymphoma cell lines. J Exp Med. 1976 Jun 1;143(6):1528–1533. doi: 10.1084/jem.143.6.1528. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ralph P., Prichard J., Cohn M. Reticulum cell sarcoma: an effector cell in antibody-dependent cell-mediated immunity. J Immunol. 1975 Feb;114(2 Pt 2):898–905. [PubMed] [Google Scholar]
  20. Rosen N., Piscitello J., Schneck J., Muschel R. J., Bloom B. R., Rosen O. M. Properties of protein kinase and adenylate cyclase-deficient variants of a macrophage-like cell line. J Cell Physiol. 1979 Jan;98(1):125–136. doi: 10.1002/jcp.1040980114. [DOI] [PubMed] [Google Scholar]
  21. Rosen N., Schneck J., Bloom B. R., Rosen O. M. Inhibition of plasminogen activator secretion by cyclic AMP in a macrophage-like cell line. J Cyclic Nucleotide Res. 1978 Oct;4(5):345–358. [PubMed] [Google Scholar]
  22. Schiff P. B., Horwitz S. B. Taxol stabilizes microtubules in mouse fibroblast cells. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1561–1565. doi: 10.1073/pnas.77.3.1561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Schneck J., Rosen O. M., Diamond B., Bloom B. R. Modulation of Fc-receptor expression and Fc-mediated phagocytosis in variants of a macrophage-like cell line. J Immunol. 1981 Feb;126(2):745–749. [PubMed] [Google Scholar]
  24. Schroder E. W., Chou I. N., Jaken S., Black P. H. Interferon inhibits the release of plasminogen activator from SV3T3 cells. Nature. 1978 Dec 21;276(5690):828–829. doi: 10.1038/276828a0. [DOI] [PubMed] [Google Scholar]
  25. Snyderman R., Pike M. C., Fischer D. G., Koren H. S. Biologic and biochemical activities of continuous macrophage cell lines P388D1 and J774.1. J Immunol. 1977 Dec;119(6):2060–2066. [PubMed] [Google Scholar]
  26. Tovey M. G., Rochette-Egly C., Castagna M. Effect of interferon on concentrations of cyclic nucleotides in cultured cells. Proc Natl Acad Sci U S A. 1979 Aug;76(8):3890–3893. doi: 10.1073/pnas.76.8.3890. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Tovey M. G., Rochette-Egly C. The effect of interferon on cyclic nucleotides. Ann N Y Acad Sci. 1980;350:266–278. doi: 10.1111/j.1749-6632.1980.tb20627.x. [DOI] [PubMed] [Google Scholar]
  28. Vandenbussche P., Divizia M., Verhaegen-Lewalle M., Fuse A., Kuwata T., De Clercq E., Content J. Enzymatic activities induced by interferon in human fibroblast cell lines differing in their sensitivity to the anticellular activity of interferon. Virology. 1981 May;111(1):11–22. doi: 10.1016/0042-6822(81)90649-8. [DOI] [PubMed] [Google Scholar]
  29. Vassef A., Beaud G., Paucker K., Lengyel P. Interferon assay based on the inhibition of double-stranded reovirus RNA accumulation in mouse L cells. J Gen Virol. 1973 Apr;19(1):81–87. doi: 10.1099/0022-1317-19-1-81. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES