Differential effect of recombinant granulocyte macrophage colony-stimulating factor on human monocytes and alveolar...

The effect of granulocyte-macrophage colony-stimulating factor (GM-CSF), a pluripotent cytokine, on tumoricidal activity of alveolar macrophages and monocytes from nonsmoking normal volunteers was compared using [3H]thymidine-labeled human tumor cells (SK-MEL-28, melanoma) as targets. A dose-response study (500-5000 units/ml) of recombinant GM-CSF indicated dramatic differences between cytotoxicity of alveolar macrophages and blood monocytes. Macrophages exhibited significant (P less than 0.01) tumoricidal activity at all GM-CSF doses tested. In contrast, monocytes showed no significant tumoricidal activity at 500 units/ml and significantly (P less than 0.01) less activity than alveolar macrophages at doses of 1000-5000 units/ml. Maximal activity in alveolar macrophages occurred 72-96 h after exposure to 1000-5000 units/ml GM-CSF. Tumoricidal activity may be related to the state of maturation, because monocytes matured in vitro for 7 days displayed enhanced tumoricidal activity after GM-CSF exposure. Tumor necrosis factor alpha and interleukin 1 beta were measured in supernatant fluids of 24-h GM-CSF-treated cells. No significant increase in either cytokine was detected after GM-CSF treatment of alveolar macrophages. Monocyte interleukin 1 beta secretion was not enhanced by GM-CSF; however, tumor necrosis factor alpha secretion was enhanced in some donors (three of five). Superoxide anion production of alveolar macrophages was not enhanced by GM-CSF. These data suggest that alveolar macrophage tumoricidal activity is induced by GM-CSF and is not dependent on oxidative metabolism or secreted forms of interleukin 1 beta or tumor necrosis factor alpha.