COMBINATIONS OF COLONY-STIMULATING FACTORS PROMOTE ENHANCED PROLIFERATIVE POTENTIAL IN ENRICHED GRANULOCYTE-MACROPHAGE COLONY-FORMING CELLS

The effects of combinations of colony-stimulating factors (CSFs) have been assessed using a highly enriched population of murine granulocyte -macrophage colony-forming cells (GM-CFC). Unlike the situation observ ed with more primitive myeloid progenitor cells, little or no effect o n the numbers of colonies formed from GM-CFC in response to specific c ombinations of growth factors was observed; however, the size of the m ajority of colonies formed was greatly increased. The largest increase in the number of cells per colony was observed when interleukin-3 (IL -3) was present with either granulocyte-macrophage colony-stimulating factor (GM-CSF), GM-CSF plus granulocyte-colony-stimulating factor (G- CSF), or macrophage colony-stimulating factor (M-CSF); there was a >fi ve-fold increase when compared to colony size in the presence of IL-3 alone. The combination of G-CSF with IL-3 was not able to promote an i ncrease in mean colony size; however, G-CSF plus GM-CSF did give a sig nificant increase. Where combinations of hematopoietic growth factors led to increased numbers of cells per colony, the delayed addition of one of the cytokines to soft gel assays for a period >2 days led to a loss of the observed enhancement in the number of cells per colony. In cultures of progenitor cells enriched by centrifugal elutriation and that contained combinations of CSFs, there was an increase in the numb er of GM-CFC over a 2-day incubation period. The distinct effects obse rved with GM-CSF, IL-3, and G-CSF on GM-CFC suggest that they influenc e different molecular signaling mechanisms within common target progen itor cells.