Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1984 Jul;50(1):97–108. doi: 10.1038/bjc.1984.144

Characterization of mouse natural killer cell activating factor (NKAF) induced by OK-432: evidence for interferon- and interleukin 2-independent NK cell activation.

O Ichimura, S Suzuki, Y Sugawara, T Osawa
PMCID: PMC1976916  PMID: 6204667

Abstract

The bacterial immunopotentiator OK-432 induced natural killer cell activating factor (NKAF) from mouse spleen cells. OK-432-induced NKAF showed a single peak with an apparent mol. wt of 70 Kd by Sephadex G-100 chromatography and OK-432-induced interleukin 2 (IL-2) had the same mol. wt as NKAF. However, OK-432-induced interferon (IFN) showed molecular heterogeneity with two peaks at 90 Kd and 45 Kd. Further purification was achieved by Blue Sepharose affinity chromatography which copurified NKAF and IFN. The affinity-purified NKAF, however, was stable to heat (56 degrees C) and acid (pH 2) treatments. Moreover, anti-IFN failed to abolish NKAF activity and this activity was not absorbed by IL-2 dependent T cells. From isoelectric focusing analysis, a dissociation of NKAF and IFN was observed over the range of pI 6.5 to 8.0. Based on these results, KNAF appears to be a new kind of cytokine distinguishable from IFN and IL-2.

Full text

PDF
97

Selected References

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

  1. Flannery G. R., Robins R. A., Baldwin R. W. Natural killer cells infiltrate transplanted chemically induced sarcomas. Cell Immunol. 1981 Jun;61(1):1–10. doi: 10.1016/0008-8749(81)90348-8. [DOI] [PubMed] [Google Scholar]
  2. Gidlund M., Orn A., Wigzell H., Senik A., Gresser I. Enhanced NK cell activity in mice injected with interferon and interferon inducers. Nature. 1978 Jun 29;273(5665):759–761. doi: 10.1038/273759a0. [DOI] [PubMed] [Google Scholar]
  3. Hanna N. Expression of metastatic potential of tumor cells in young nude mice is correlated with low levels of natural killer cell-mediated cytotoxicity. Int J Cancer. 1980 Nov 15;26(5):675–680. doi: 10.1002/ijc.2910260521. [DOI] [PubMed] [Google Scholar]
  4. Henney C. S., Kuribayashi K., Kern D. E., Gillis S. Interleukin-2 augments natural killer cell activity. Nature. 1981 May 28;291(5813):335–338. doi: 10.1038/291335a0. [DOI] [PubMed] [Google Scholar]
  5. Herberman R. B., Ortaldo J. R., Mantovani A., Hobbs D. S., Kung H. F., Pestka S. Effect of human recombinant interferon on cytotoxic activity of natural killer (NK) cells and monocytes. Cell Immunol. 1982 Feb;67(1):160–167. doi: 10.1016/0008-8749(82)90208-8. [DOI] [PubMed] [Google Scholar]
  6. Heron I., Hokland M., Møller-Larsen A., Berg K. The effect of interferon on lymphocyte-mediated effector cell functions: selective enhancement of natural killer cells. Cell Immunol. 1979 Jan;42(1):183–187. doi: 10.1016/0008-8749(79)90232-6. [DOI] [PubMed] [Google Scholar]
  7. Kaiserlian D., Bardos P., Bach J. F. In vitro modulation of mouse natural killer (NK) cell activity by the serum thymic factor (FTS). Cell Immunol. 1983 Mar;76(2):232–242. doi: 10.1016/0008-8749(83)90366-0. [DOI] [PubMed] [Google Scholar]
  8. Koi M., Saito M., Ebina T., Ishida N. Lactate dehydrogenase-elevating agent is responsible for interferon induction and enhancement of natural killer cell activity by inoculation of Ehrlich ascites carcinoma cells into mice. Microbiol Immunol. 1981;25(6):565–574. doi: 10.1111/j.1348-0421.1981.tb00058.x. [DOI] [PubMed] [Google Scholar]
  9. Langford M. P., Weigent D. A., Georgiades J. A., Johnson H. M., Stanton G. J. Antibody to staphylococcal enterotoxin A-induced human immune interferon (IFN gamma). J Immunol. 1981 Apr;126(4):1620–1623. [PubMed] [Google Scholar]
  10. Moore K., Moore M. Systemic and in-situ natural killer activity in tumour-bearing rats. Br J Cancer. 1979 Jun;39(6):636–647. doi: 10.1038/bjc.1979.115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Oshimi K., Kano S., Takaku F., Okumura K. Augmentation of mouse natural killer cell activity by a streptococcal preparation, OK-432. J Natl Cancer Inst. 1980 Dec;65(6):1265–1269. [PubMed] [Google Scholar]
  12. Saito M., Ebina T., Koi M., Yamaguchi T., Kawade Y., Ishida N. Induction of interferon-gamma in mouse spleen cells by OK-432, a preparation of Streptococcus pyogenes. Cell Immunol. 1982 Mar 15;68(1):187–192. doi: 10.1016/0008-8749(82)90102-2. [DOI] [PubMed] [Google Scholar]
  13. Saito M., Yamaguchi T., Ebina T., Koi M., Aonuma E., Usami H., Ishida N. In vitro production of immune interferon (IFN gamma) by murine spleen cells when different sensitizing antigens are used in vivo and in vitro. Cell Immunol. 1983 Jun;78(2):379–386. doi: 10.1016/0008-8749(83)90293-9. [DOI] [PubMed] [Google Scholar]
  14. Stefanos S., Catinot L., Wietzerbin J., Falcoff E. Production of antibodies against mouse immune T (type II) interferon and their neutralizing properties. J Gen Virol. 1980 Sep;50(1):225–229. doi: 10.1099/0022-1317-50-1-225. [DOI] [PubMed] [Google Scholar]
  15. Talmadge J. E., Meyers K. M., Prieur D. J., Starkey J. R. Role of NK cells in tumour growth and metastasis in beige mice. Nature. 1980 Apr 17;284(5757):622–624. doi: 10.1038/284622a0. [DOI] [PubMed] [Google Scholar]
  16. Uchida A., Micksche M. In vitro augmentation of natural killing activity by OK-432. Int J Immunopharmacol. 1981;3(4):365–375. doi: 10.1016/0192-0561(81)90032-1. [DOI] [PubMed] [Google Scholar]
  17. Uchida A., Micksche M. Intrapleural administration of OK432 in cancer patients: activation of NK cells and reduction of suppressor cells. Int J Cancer. 1983 Jan 15;31(1):1–5. doi: 10.1002/ijc.2910310102. [DOI] [PubMed] [Google Scholar]
  18. Uchida A., Micksche M. Lysis of fresh human tumor cells by autologous large granular lymphocytes from peripheral blood and pleural effusions. Int J Cancer. 1983 Jul 15;32(1):37–44. doi: 10.1002/ijc.2910320107. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES