Dual activity of CSF-1, produced by a murine hybrid cell line and from other sources, on the growth of bone marrow stromal cells in culture.

Medium conditioned by the cell line A.4.10 was shown to produce a factor that inhibits the growth of bone marrow (BM) stromal foci in liquid cultures. In this study we demonstrated that CSF-1, present in this conditioned medium (CM), was largely responsible for this inhibition. This was concluded from the following findings: 1) the CSF-1 activity in the CM copurified with the inhibitory activity in several biochemical purification procedures; 2) an antibody against murine CSF-1 was able to neutralize the CSF-1 activity as well as the inhibitory activity in the A.4.10 CM; and 3) immunopurified murine CSF-1 from A.4.10 CM and from another murine source and recombinant human (rh) CSF-1 were all able to inhibit stromal cell growth. In secondary stromal cultures, inhibition was demonstrated at high cell densities but not at low densities, suggesting that accessory cells may be involved in the effect. When the dose rh CSF-1 was reduced to half of that required to produce 50% inhibition, stimulation of primary stromal foci growth was demonstrated, supporting observations by others that CSF-1 can act as a growth factor for BM stromal cells. In this report we thus demonstrate both inhibitory and stimulatory effects of CSF-1 on the growth of BM stromal cells in vitro.