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Leukemic cell lysis by activated human macrophages: significance of membrane-associated tumor necrosis factor

Y Nakabo1, N Harakawa, K Yamamoto

  • 1Department of Internal Medicine, Faculty of Medicine, Kyoto University.

Japanese Journal of Cancer Research : Gann
|November 1, 1993
PubMed

Insights

Human macrophages activated with interferon-gamma and lipopolysaccharide kill leukemic cells. This cell-mediated cytotoxicity relies on cell-associated tumor necrosis factor (TNF), not secreted TNF.

Area of Science:

  • Immunology
  • Cell Biology
  • Cancer Research

Background:

  • Macrophages are key immune cells involved in tumor surveillance.
  • Understanding macrophage-mediated cytotoxicity is crucial for developing novel cancer therapies.
  • Leukemic cells present a unique challenge due to their resistance to conventional treatments.

Purpose of the Study:

  • To elucidate the mechanisms by which activated human macrophages lyse leukemic cells.
  • To investigate the role of tumor necrosis factor (TNF) in macrophage-induced leukemic cell death.

Main Methods:

  • Peripheral blood monocyte-derived macrophages were activated using recombinant interferon-gamma and lipopolysaccharide.
  • Lytic activity against K562 and HL-60 leukemic cell lines was measured using an 111In releasing assay.
  • The effect of anti-tumor necrosis factor (TNF) antibody on macrophage-mediated lysis was evaluated.

Main Results:

  • Activated macrophages demonstrated significant lytic activity against K562 and HL-60 cells.
  • Macrophage-derived lysates also exhibited cytotoxicity against leukemic cells.
  • Lytic activity was significantly inhibited by anti-TNF antibody, indicating TNF's involvement.
  • Leukemic cell lines used were resistant to recombinant TNF, and no lysis was observed in culture supernatants.

Conclusions:

  • Cell-associated tumor necrosis factor (TNF) plays a critical role in the cytotoxicity of activated macrophages against leukemic cells.
  • The findings suggest a targeted mechanism involving cell-surface TNF rather than secreted factors.
  • This study provides insights into macrophage-based immunotherapy strategies for leukemia.

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