Colony-stimulating factor (CSF-1): Its enhancement of plasminogen activator production and inhibition of cell growth in a mouse macrophage cell line

CSF-1 is a hematopoietic growth factor that specifically causes the proliferation and differentiation of mononuclear phagocytic cells. J774 cells are a monocyte precursor-like macrophage cell line. This transformed macrophage cell line exhibits specific ¹²⁵I-CSF-1-binding activity similar to that of normal murine macrophages, although its survival and growth is independent of CSF-1. At 0°C, saturation of binding sites was achieved at 250 pM ¹²⁵I-CSF-1. At 37° C, the bound ¹²⁵I-CSF-1 was rapidly internalized and degraded by the target cells with a T( 1/2 ) of approximately 30 min; degradation was inhibited by the addition of NH₄Cl. The addition of CSF-1 to cultures caused dose-dependent inhibition rather than stimulation of [³H]thymidine uptake by J774 cells. Whereas CSF-1 stimulated the clonal growth of normal mouse peritoneal exudate macrophages, it inhibited the clonal growth of J774 cells in agar cultures. Furthermore, CSF-1 exhibited a concentration-dependent enhancement of the production of plasminogen activator (PA) by J774 cells. The enhanced production of PA was detected 6 hr after the addition of CSF-1 and was inhibited by the simultaneous addition of the anti-inflammatory drug. It appears that the effects of CSF-1 on cell proliferation and PA production by CSF-1 receptor-bearing cells are mediated by distinct intracellular pathways albeit through the same receptor.