Induction of reactive oxygen intermediates in human monocytes by tumour cells and their role in spontaneous monocyte cytotoxicity

Br J Cancer. 1999 Feb;79(5-6):737-43. doi: 10.1038/sj.bjc.6690118.

Abstract

The present study examined the ability of human monocytes to produce reactive oxygen intermediates after a contact with tumour cells. Monocytes generated oxygen radicals, as measured by luminol-enhanced chemiluminescence and superoxide anion production, after stimulation with the tumour, but not with untransformed, cells. The use of specific oxygen radical scavengers and inhibitors, superoxide dismutase, catalase, dimethyl sulphoxide and deferoxamine as well as the myeloperoxidase inhibitor 4-aminobenzoic acid hydrazide, indicated that chemiluminescence was dependent on the production of superoxide anion and hydroxyl radical and the presence of myeloperoxidase. The tumour cell-induced chemiluminescent response of monocytes showed different kinetics from that seen after activation of monocytes with phorbol ester. These results indicate that human monocytes can be directly stimulated by tumour cells for reactive oxygen intermediate production. Spontaneous monocyte-mediated cytotoxicity towards cancer cells was inhibited by superoxide dismutase, catalase, deferoxamine and hydrazide, implicating the role of superoxide anion, hydrogen peroxide, hydroxyl radical and hypohalite. We wish to suggest that so-called 'spontaneous' tumoricidal capacity of freshly isolated human monocytes may in fact be an inducible event associated with generation of reactive oxygen intermediates and perhaps other toxic mediators, resulting from a contact of monocytes with tumour cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma
  • Carcinoma, Hepatocellular
  • Cell Division*
  • Cell Line
  • Cell Survival*
  • Female
  • Flow Cytometry
  • Humans
  • Liver Neoplasms
  • Luminescent Measurements
  • Monocytes / cytology
  • Monocytes / drug effects
  • Monocytes / physiology*
  • Ovarian Neoplasms
  • Pancreatic Neoplasms
  • Reactive Oxygen Species / physiology*
  • Superoxides / blood
  • Tumor Cells, Cultured

Substances

  • Reactive Oxygen Species
  • Superoxides