Proliferative effects of purified granulocyte colony‐stimulating factor (G‐CSF) on normal mouse hemopoietic cells

When granulocyte colony‐stimulating factor (G‐CSF), purified to homogeneity from mouse lung‐conditioned medium, was added to agar cultures of mouse bone marrcw cells, it stimulated the formation of small numbers of granulocytic colonies. At high concentrations of G‐CSF, a small proportion of macrophage and granulocyte‐macrophage colonies also developed. G‐CSF stimulated colony formation by highly enriched progenitor cell populations obtained by fractionation of mouse fetal liver cells using a fluorescence‐activated cell sorter, indicating that G‐CSF probably acts directly on target progenitor cells. Granulocytic colonies stimulated by G‐CSF were small and uniform in size, and at 7 days of culture were composed of highly differentiated cells. Studies using clonal transfer and the delayed addition of other regulators showed that G‐CSF could directly stimulate the initial proliferation of a large proportion of the granulocvte‐macrophage progenitors in adult marrow and also the survival and/or proliferation of some multipotential, erythroid, and eosinophil progenitors in fetal liver. However, G‐CSF was unable to sustain continued proliferation of these cells to result in colony formation. When G‐CSF was mixed with purified granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) or macrophage colony‐stimulating factor (M‐CSF), the combination stimulated the formation by adult marrow cells of more granulocyte‐macrophage colonies than either stimulus alone and an overall size increase in all colonies. G‐CSF behaves as a predominantly granulopoietic stimulating factor but has some capacity to stimulate the initial proliferation of the same wide range of progenitor cells as that stimulated by GM‐CSF.