Skip to main content
Log in

Monocyte-mediated drug-dependent cellular cytotoxicity: effects on different WEHI 164 Target cell lines

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

Summary

The contribution of monocyte cytotoxic protein factor (CF) to monocyte-mediated drug-dependent cellular cytotoxicity (DDCC) has been investigated. Cell lines which have been derived from murine WEHI 164 cells (termed WEHI 164 parental) by selecting for high (WEHI 164 clone 3) and low (R-WEHI 164) sensitivity to CF-mediated cytotoxicity were used as target cells in DDCC. By comparing the CF doses which produced 50% dead cells (LD 50) we found that WEHI 164 clone 3 was approximately 30 times more sensitive than WEHI 164 parental which in turn was 70 times more sensitive than R-WEHI 164. Actinomycin D (Act D) treatment of WEHI 164 parental and R-WEHI 164 greatly increase susceptibility to CF-mediated cytotoxicity. The susceptibility of WEHI 164 clone 3 was apparently somewhat increased at low dilutions of CF, whereas no significant increase was observed at high dilutions. The susceptibility to DDCC of the three target cell lines (WEHI 164 parental, WEHI 164 clone 3, and R-WEHI 164) correlated with the sensitivity pattern obtained in CF-mediated cytotoxicity of Act D-treated target cells. Monocyte- and CF-mediated cytotoxicity against Act D-treated WEHI 164 clone 3 and R-WEHI 164 was inhibited by neutralizing CF antiserum. These data indicate that CF is an effector molecule in monocyte-mediated DDCC.

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. Aggarwal BB, Kohr WJ, Hass PE, Moffat B, Spencer SA, Henzel WJ, Bringman TS, Nedwin GE, Goeddel DV, Harkins RN (1985) Human tumor necrosis factor. Production, purification, and characterization. J Biol Chem 260:2345

    Google Scholar 

  2. Austgulen R, Hammerstrøm J, Espevik T, Nissen-Meyer J (1986) Human monocyte cytotoxic factor mediates cytolysis of WEHI 164 cells. Cell Immunol 98:211

    Google Scholar 

  3. Cameron DJ, Churchill WH (1979) Cytotoxicity of human macrophages for tumour cells. Enhancement by lymphocyte mediators. J Clin Invest 63:977

    Google Scholar 

  4. Colotta F, Peri G, Villa A, Mantovani A (1984) Rapid killing of actinomycin D-treated tumor cells by human mononuclear cells. 1. Effectors belong to the monocyte-macrophage line-age. J Immunol 132:936

    Google Scholar 

  5. Espevik T (1985) Human monocyte-mediated lysis of antibody-coated tumor cells: The role of the cytoskeleton in monocytes. J Immunol 134:2017

    Google Scholar 

  6. Espevik T, Kildahl-Andersen O, Nissen-Meyer J (1986) The role of monocyte cytotoxic factor (CF) in monocyte-mediated lysis of tumor cells. Immunology 57:255

    Google Scholar 

  7. Freundlich B, Trinchieri G, Perussia B, Zurier RB (1984) The cytotoxic effector cells in preparations of adherent mononuclear cells from human peripheral blood. J Immunol 132:1255

    Google Scholar 

  8. Hammerstrøm J (1979) Human macrophage differentiation in vivo and in vitro. A comparison of human peritoneal macrophages and monocytes. Acta Pathol Microbiol Immunol Scand [C] 87:113

    Google Scholar 

  9. Hammerstrøm J (1979) In vitro influence of endotoxin on human mononuclear phagocyte structure and function. Enhancement of the expression of cytostatic and cytolytic activity of normal and lymphokine-activated monocytes. Acta Pathol Microbiol Immunol Scand [C] 87:391

    Google Scholar 

  10. Hammerstrøm J (1979) Human monocyte-mediated cytotoxicity to K-562 cells: activation by lymphokines. Scand J Immunol 10:575

    Google Scholar 

  11. Hammerstrøm J (1981) Human adherent mononuclear blood cells: Cytolytic and cytostatic activity and characterization of effector cells during in vitro culture. Acta Pathol Microbiol Immunol Scand [C] 89:115

    Google Scholar 

  12. Kildahl-Anderson O, Nissen-Meyer J (1985) The role of monocyte cytotoxic factor (CF) in cytostasis mediated by IFN-gamma-activated monocytes. Immunology 56:367

    Google Scholar 

  13. Kildahl-Andersen O, Nissen-Meyer J (1985) Production and characterization of cytostatic protein factors released from human monocytes during exposure to lipopolysaccharide (LPS) and muramyl dipeptide (MDP). Cell Immunol 93:375

    Google Scholar 

  14. Kildahl-Andersen O, Austgulen R, Nissen-Meyer J (1986) WEHI 164 sarcoma cells rendered resistant to monocyte-released cytotoxin are also resistant to monocyte-induced cytolysis. Cancer Immunol Immunother 21:77

    Google Scholar 

  15. Löms Zielger-Heitbrock HW, Rietmuller G (1984) A Rapid assay for cytotoxicity of unstimulated human monocytes. J Natl Cancer Inst 72:23

    Google Scholar 

  16. Mantovani A, Dean JH, Jerrells TR, Herberman RB (1980) Augmentation of tumoricidal activity of human monocytes and macrophages by lymphokines. Int J Cancer 25:691

    Google Scholar 

  17. Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J Immunol Methods 65:55

    Article  PubMed  Google Scholar 

  18. Nissen-Meyer J, Kildahl-Andersen O (1984) Purification of cytostatic protein factors released from human monocytes. Scand J Immunol 20:317

    Google Scholar 

  19. Pennica D, Nedwin GE, Hayflick JS, Seeburg PH, Derynck R, Palladino MA, Kohr WJ, Aggarwal BB, Goeddel DV (1984) Human tumor necrosis factor: precursor structure, expression and homology to lymphotoxin. Nature 312:724

    Google Scholar 

  20. Röllinghoff M, Warner NL (1973) Specificity of in vivo tumor rejection assessed by mixing immune spleen cells with target and unrelated tumor cells. Proc Soc Exp Biol Med 144:813

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Austgulen, R., Kildahl-Andersen, O. & Espevik, T. Monocyte-mediated drug-dependent cellular cytotoxicity: effects on different WEHI 164 Target cell lines. Cancer Immunol Immunother 22, 176–180 (1986). https://doi.org/10.1007/BF00200029

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00200029

Keywords

Navigation