SHORT COMMUNICATION: Bone Marrow Progenitors Cultured in the Presence of Granulocyte-Macrophage Colony-Stimulating Factor Versus Macrophage Colony-Stimulating Factor Differentiate Into Macrophages With Distinct Tumoricidal Capacities

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Abstract
Bone marrow-derived cells from C3H/HeJ mice were cultured in the presence of recombinant murine granulocyte-macrophage colony-stimulating factor (rGM-CSF) or highly purified murine macrophage colony-stimulating factor (CSF-1) for 7 days. Following this 7-day culture period, mature macrophages were harvested and replated at precise densities in the absence of exogenous rGM-CSF or CSF-1, and assayed in a two-signal tumoricidal assay. Cultures were stimulated with medium only or with combinations of recombinant interferon-γ (rIFN-γ) as the “priming” signal, and/or butanol-extracted lipopolysaccharide (But-LPS) as the “triggering” signal for 24 hr. At this time, 51Cr-labeled, P815 tumor target cells were added, and the percent tumor cell cytotoxicity was determined after 16 hr. Macrophages derived under the influence of rGM-CSF exhibited significant tumoricidal capacity with medium alone (16 ± 5%). The addition of “priming” signal only (i.e., rIFN-γ, 10.0 U/ml) significantly increased tumoricidal capacity to 31 ± 9%. Treatment with But-LPS alone did not alter the basal tumoricidal activity of rGM-CSF-derived macrophages. Combinations of rIFN-γ (10.0 U/ml) and But-LPS (0.5–5.0 μg/ml) generated highly tumoricidal macrophages (50-60% tumor cell cytotoxicity). In contrast, medium-treated CSF-1-derived macrophages exhibited a significantly lower basal level of tumor cytotoxicity (6 ± 3%). Unlike rGM-CSF-derived macrophages, treatment of CSF-1-derived macrophages with high concentrations of rIFN-γ alone did not increase significantly the level of cytotoxicity above that of medium-treated cultures. However, CSF-1-derived macrophages responded to the highest concentrations of But-LPS (5.0 νg/ml) to increase tumoricidal activity from 6 ± 3% to 17 ± 5%. Optimal tumoricidal activity (44 ± 17%) was observed when CSF-1-derived macrophages were treated simultaneously with high concentrations of both rIFN-γ and But-LPS. Thus, macrophages derived from bone marrow progenitors in either rGM-CSF or CSF-1 exhibited tumoricidal capacities that differed in basal activity as well as in their requirements for and sensitivities to “priming” and “triggering” signals.