Modulation of human alveolar macrophage tumoricidal activity by recombinant macrophage colony-stimulating factor

Recombinant macrophage colony-stimulating factor (M-CSF) is a hemopoietic growth factor capable of modulating activities of both immature and mature monocytes. The effect of M-CSF 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 (500-5,000 U/ml) of recombinant M-CSF indicated that both alveolar macrophages and blood monocytes demonstrated peak cytotoxicity at 1,000 U/ml. Maximal activity occurred 72-96 h after exposure to 1,000 U/ml of M-CSF. To investigate the mechanisms involved in this cytotoxicity, tumor necrosis factor-alpha (TNF) and interleukin-1-beta (IL-1) were measured in supernatant fluids of 24 h M-CSF-treated cells. No significant increase in either cytokine was detected after M-CSF treatment of alveolar macrophages or monocytes. Superoxide anion production of alveolar macrophages was not enhanced by M-CSF. These data suggest that alveolar macrophages tumoricidal activity is induced by M-CSF and is not dependent on oxidative metabolism or secreted forms of IL-1 or TNF.