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Enhancing effect of human monocytic colony-stimulating factor on monocyte tumoricidal activity
1Biochemical Research Laboratory, Morinaga Milk Industry Co., Ltd., Tokyo, Japan.
Abstract:
Human monocytic colony-stimulating factor (hM-CSF) enhances several effector functions of human peripheral blood monocytes. In this study, we investigated the effect of the Mr 85,000 form of hM-CSF on the tumoricidal activity of human monocytes against several leukemic cell lines using a 12-h chromium release assay. Human peripheral blood monocytes preincubated with hM-CSF for 48 h showed more effective killing activity towards K562, U937, Daudi, and HL60 cells as compared with the cells preincubated with medium alone. Maximal enhancement of the tumoricidal activity was achieved by hM-CSF at concentrations of 50-100 ng/ml. A trace amount of lipopolysaccharide contained in the hM-CSF did not seem to contribute to the enhancing effect, as the addition of a lipopolysaccharide-neutralizing agent, polymyxin B, to the preincubation mixture did not reduce this effect. Anti-tumor necrosis factor antiserum partially blocked the tumoricidal activity mediated by hM-CSF, indicating that tumor necrosis factor may participate in the hM-CSF-mediated increase of monocyte tumor cell-killing activity. These results suggest that in addition to other monocyte-activating factors, hM-CSF augments monocyte tumoricidal activity against a wide spectrum of tumor targets.
Insights
Human monocytic colony-stimulating factor (hM-CSF) significantly boosts monocyte tumoricidal activity against various leukemia cell lines. This enhancement, observed after 48-hour preincubation, suggests hM-CSF as a potential therapeutic agent.
Area of Science:
- Immunology
- Cell Biology
- Cancer Research
Background:
- Human monocytic colony-stimulating factor (hM-CSF) is known to enhance monocyte effector functions.
- Monocytes play a crucial role in the immune response against cancer cells.
Purpose of the Study:
- To investigate the effect of hM-CSF on the tumoricidal activity of human monocytes against leukemic cell lines.
- To determine the optimal concentration of hM-CSF for enhancing monocyte anti-tumor activity.
Main Methods:
- A 12-hour chromium release assay was used to measure tumoricidal activity.
- Human peripheral blood monocytes were preincubated with varying concentrations of hM-CSF.
- The role of lipopolysaccharide and tumor necrosis factor was assessed using polymyxin B and anti-tumor necrosis factor antiserum.
Main Results:
- hM-CSF preincubation significantly enhanced monocyte killing of K562, U937, Daudi, and HL60 cells.
- Maximal enhancement of tumoricidal activity was observed at hM-CSF concentrations of 50-100 ng/ml.
- Tumor necrosis factor partially mediated the hM-CSF-induced increase in monocyte tumoricidal activity.
Conclusions:
- hM-CSF augments the tumoricidal activity of human monocytes against a broad spectrum of tumor targets.
- The enhancing effect is not attributed to trace amounts of lipopolysaccharide.
- Tumor necrosis factor may play a role in hM-CSF-mediated monocyte anti-tumor effects.