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 hemopoietic 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-I-binding activity similar to that of normal murine macrophages, although its survival and growth is independent of CSF-1. At 0 degrees C, saturation of binding sites was achieved at 240 pM 125I-CSF-1. At 37 degrees C, the bound 125I-CSF-1 was rapidly internalized and degraded by the target cells with a T1/2 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.
D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002999:Clone Cells / Q000378:metabolism / Q000473:pathology; D003115:Colony-Stimulating Factors / Q000378:metabolism / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D008074:Lipoproteins / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D010960:Plasminogen Activators / Q000096:biosynthesis*; D011506:Proteins; D011956:Receptors, Cell Surface / Q000032:analysis; D016184:Receptors, Colony-Stimulating Factor
D003115:Colony-Stimulating Factors; D008074:Lipoproteins; D011506:Proteins; D011956:Receptors, Cell Surface; D016184:Receptors, Colony-Stimulating Factor; C016313:colony inhibiting factor; D004247:DNA; D010960:Plasminogen Activators