Enhanced responsiveness of committed macrophage precursors to macrophage-type colony-stimulating factor (CSF-1)...

Contrasting effects of interferon alpha + beta (IFN) on colony-stimulating factor- (CSF) induced macrophage stem cell proliferation resulted when nucleated murine femoral marrow cells were exposed to IFN either before addition of CSF or simultaneously with CSF. Responsiveness to macrophage type L cell CSF was measured by two different assays: by determination of [3H]thymidine (3H-TdR) incorporation and by enumeration of colonies formed in response to CSF. Incubation of nucleated marrow cells concurrently with CSF and IFN resulted in depressed proliferation that was dependent on the dose of IFN. Preincubation of marrow cells with IFN, however, produced a dose-dependent enhancement of CSF responsiveness in comparison to preincubation of marrow cells in the absence of IFN. The enhancing effect of IFN was observed only when preincubated cells were stimulated with suboptimal concentrations of CSF. At optimal CSF concentrations, differences were not observed in either 3H-TdR incorporation or in colony formation. On the basis of data accumulated by both assays for CSF responsiveness, IFN pretreatment was hypothesized not to increase the total population of existing progenitor cells, but to influence the capacity of pre-existing progenitor cells to respond to suboptimal doses of the growth factor.