Skip to main content
Log in

AViscum album oligosaccharide activating human natural cytotoxicity is an interferon γ inducer

  • Original articles
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Summary

CommercialViscum album extract Helixor-M contains a dialysable oligosaccharide (HM-BP) that activates natural killer (NK) cytotoxicity against K562 tumour cells when preincubated with human peripheral blood mononuclear cells (PBMC) for 72 h. The activated effector cells were exclusively found in the monocyte/macrophage subpopulation. However, when peripheral non-adherent cells (PNAC) were preincubated with HM-BP for 72 h the NK cytotoxicity of CD56+CD3 NK cells was activated. This discrepancy was found to be due to the release of prostaglandin E2 from activated monocytes/macrophages, which blocked activation of the cytotoxicity of NK cells. Analysis of the supernatant culture medium after 72 h preincubation demonstrated that HM-BP induced release of interferon γ (IFNγ) from T cells (preferentially from CD3+CD4+ cells) and of tumour necrosis factor α (TNFα) from monocytes/macrophages. Release of IFNγ was the crucial step for activation of NK cytotoxicity since enhancement of NK cytotoxicity during pretreatment of PBMC or PNAC with HM-BP was completely blocked in the presence of anti-IFNγ antibodies. Anti-interleukin-2, anti-TNFα or anti-IFNα antibodies had no effect on the HM-BP-induced enhancement of NK cytotoxicity. The activation of the NK cytotoxicity of nonadherent cells by interleukin-2 treatment was found to be synergistic to the enhancement of NK cytotoxicity by treatment with HM-BP.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Adams DO, Hamilton TA (1984) The cell biology of macrophage activation. Annu Rev Immunol 2: 283–318

    Google Scholar 

  2. Bode C, Ganzhorn A, Brauner B, Bode JC (1989) Effect of acute ethanol ingestion on human gastric luminal prostaglandin E2, prostaglandin F2α and 6-keto-prostaglandin F1α. Alcohol Alcoholism 24: 35–42

    Google Scholar 

  3. Bonavida B, Bradley TP, Grimm EA (1983) Frequency determination of killer cells by single-cell cytotoxic assay. Methods Enzymol 93: 270–280

    Google Scholar 

  4. Bøyum A (1968) Isolation of mononuclear cells and granulocytes from human blood. Scand J Clin Lab Invest 21 [Suppl 97]: 77–89

    Google Scholar 

  5. Damle NK, Doyle LV, Bradley EC (1986) Interleukin-2-activated human killer cells are derived from phenotypically heterogenous precursors. J Immunol 137: 2814–2822

    Google Scholar 

  6. Dinarello CA (1987) The biology of interleukin 1 and comparison to tumor necrosis factor. Immunol Lett 16: 227–232

    Google Scholar 

  7. Doyle MV, Lee MT, Fong S (1985) Comparison of the biological activities of human recombinant interleukin 2 and native interleukin 2. J Biol Response Mod 4: 96–109

    Google Scholar 

  8. Dray F, Charbonne LB, MacLouf J (1975) Radioimmunoassay of prostaglandins F2, E1, E2 in human plasma. Eur J Clin Invest 5: 311–318

    Google Scholar 

  9. Einhorn S, Blomgren H, Strander H (1978) Interferon and spontaneous cytotoxicity in man: I. Enhancement of the spontaneous cytotoxicity of peripheral lymphocytes by human interferon. Int J Cancer 22: 405–412

    Google Scholar 

  10. Foon KA (1989) Biological response modifiers: the new immunotherapy. Cancer Res 49: 1621–1639

    Google Scholar 

  11. Gerrard TL, Terz JJ, Kaplan AM (1980) Cytotoxicity to tumor cells of monocytes from normal individuals and cancer patients. Int J Cancer 26: 585–593

    Google Scholar 

  12. Gibson PR, Hermanowicz A, Jewell DP (1984) Factors affecting the spontaneous cell-mediated cytotoxicity of intestinal mononuclear cells. Immunology 53: 267–274

    Google Scholar 

  13. Hamprecht K, Voetsch W, Anderer FA (1986) Activation of human monocyte and natural killer cell-mediated cell killing by two dialyzable thymic factors. Scand J Immunol 24: 59–71

    Google Scholar 

  14. Hamprecht K, Handgretinger R, Voetsch W, Anderer FA (1987) Mediation of human NK activity by compounds in extracts ofViscum album. Int J Immunopharmacol 9: 199–209

    Google Scholar 

  15. Herberman RB (1987) Cancer therapy by biological response modifiers. Clin Physiol Biochem 5: 238–248

    Google Scholar 

  16. Herberman RB, Ortaldo JR, Bonnard GD (1979) Augmentation by interferon of human natural and antibody-dependent cell-mediated immunity. Nature 277: 221–223

    Google Scholar 

  17. Ibayashi Y, Hoon DSB, Golub SH (1987) The regulatory effect of adherent cells on lymphokine activated killer cells. Cell Immunol 110: 365–378

    Google Scholar 

  18. Jordan E, Wagner H (1986) Structure and properties of polysaccharides fromViscum album (L.) Oncology 43 [Suppl 1]: 8–15

    Google Scholar 

  19. Kimber I, Moore M (1985) Mechanism and regulation of natural cytotoxicity. Exp Cell Biol 53: 69–84

    Google Scholar 

  20. Klett CY, Anderer FA (1989) Activation of natural killer cell cytotoxicity of human blood monocytes by a low molecular weight component fromViscum album extract. Arzneim-Forsch/Drug Res 39: 1580–1585

    Google Scholar 

  21. Koff WC, Fogler WE, Gutterman J, Fidler IJ (1985) Efficient activation of human blood monocytes to a tumoricidal state by liposomes containing human recombinant gamma interferon. Cancer Immunol Immunother 19: 85–89

    Google Scholar 

  22. Korzeniewski C, Callewaert DM (1983) An enzyme release assay for natural cytotoxicity. J Immunol Methods 64: 313–332

    Google Scholar 

  23. Krisnamurti C, Ahrens P, Ankel H (1987) Differential effects of beta and gamma interferons on natural killer cell mediated lysis of lung carcinoma cells. Immunobiology 174: 221–232

    Google Scholar 

  24. Lanier LL, Phillips JH (1988) Effectors, repertoire and receptors involved in lymphocyte-mediated MHC-unrestricted cytotoxicity. Ann Inst Pasteur Immunol 139: 450–456

    Google Scholar 

  25. Leighton JD, Pfeilschifter J (1990) Interleukin 1- and tumor necrosis factor-stimulation of prostaglandin E2 synthesis in MDCK cells, and potentiation of this effect by cycloheximide. FEBS Lett 259: 289–292

    Google Scholar 

  26. Leung KH (1989) Inhibition of human NK cell and LAK cell cytotoxicity and differentiation by PGE2. Cell Immunol 123: 384–395

    Google Scholar 

  27. Leung KH, Koren HS (1982) Regulation of human natural killing: II. Protective effect of interferon on NK cells from suppression by PGE2. J Immunol 129: 1742–1747

    Google Scholar 

  28. Lozzio CB, Lozzio BB (1975) Human chronic myelogenous leukemia cell line with positive Philadelphia chromosome. Blood 45: 321–334

    Google Scholar 

  29. Milteny S, Müller W, Weichsel W, Radbruch A (1990) High gradient magnetic cell separation with MACS — alternative and complementation to fluorescence activated cell sorting. Cytometry 11b (in press)

  30. Mueller EA, Hamprecht K, Anderer FA (1989) Biochemical characterization of a component in extracts ofViscum album enhancing human NK cytotoxicity. Immunopharmacology 17: 11–18

    Google Scholar 

  31. Mueller EA, Hamprecht K, Anderer FA (1990) A galacturonic acid-containing polysaccharide in extracts ofViscum album enhances human NK cytotoxicity. In: Proc VI Int Natural Killer Workshop 1989. Karger, Basel (in press)

    Google Scholar 

  32. Ortaldo JR, Longo DL (1988) Human natural lymphocyte effector cells: definition, analysis of activity and clinical effectiveness. J Natl Cancer Inst 80: 999–1010

    Google Scholar 

  33. Ortaldo JR, Mason A, Overton R (1986) Lymphokine-activated killer cells. J Exp Med 164: 1193–1205

    Google Scholar 

  34. Patel SS, Thiele DL, Lipsky PE (1987) Major histocompatibility complex-unrestricted cytolytic activity of human T cells: analysis of precursor frequency and effector phenotype. J Immunol 139: 3886–3895

    Google Scholar 

  35. Pflueger E, Mueller EA, Anderer FA (1990) Preservation of cytotoxic function during multi-cycle immunomagnetic cell separations of human NK cells using a new type of magnetic bead. J Immunol Methods 129: 165–173

    Google Scholar 

  36. Phillips JH, Lanier LL (1986) Dissection of lymphokine-activated killer cells. J Exp Med 164: 814–825

    Google Scholar 

  37. Rosenberg SA, Grimm EA, McGrogan M, Doyle M, Kawasaki E, Koths K, Mark DF (1984) Biological activity of recombinant human interleukin 2 produced inE. coli. Science 223: 1412–1415

    Google Scholar 

  38. Tilden AB, Itoh K, Balch CM (1987) Human lymphokine-activated killer cells. Identification of two types of effector cells. J Immunol 138: 1068–1073

    Google Scholar 

  39. Timonen T, Saksela E, Ranki A, Häyry P (1979) Fractionation, morphological and functional characterization of effector cells responsible for human natural killer activity against cell-line targets. Cell Immunol 48: 133–148

    Google Scholar 

  40. Toledano M, Mathiot C, Michon J, Andreu G, Lando D, Brandely M, Fridman WH (1989) Interferon-γ and interleukin-2 in the generation of lymphokine-activated killer cytotoxicity: interferon-γ-induced suppressive activity. Cancer Immunol Immunother 30: 57–64

    Google Scholar 

  41. Wang A, Lu SD, Nark DF (1984) Site specific mutagenesis of the human interleukin 2 gene: structure function analysis of the cysteine residues. Science 224: 1431–1433

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mueller, E.A., Anderer, F.A. AViscum album oligosaccharide activating human natural cytotoxicity is an interferon γ inducer. Cancer Immunol Immunother 32, 221–227 (1990). https://doi.org/10.1007/BF01741704

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01741704

Keywords

Navigation