Combinations of colony-stimulating factors promote enhanced proliferative potential in enriched granulocyte-macrophage colony-forming cells.

Abstract

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 observed with more primitive myeloid progenitor cells, little or no effect on the numbers of colonies formed from GM-CFC in response to specific combinations of growth factors was observed; however, the size of the majority 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 > five-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 increase in mean colony size; however, G-CSF plus GM-CSF did give a significant 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 number of GM-CFC over a 2-day incubation period. The distinct effects observed with GM-CSF, IL-3, and G-CSF on GM-CFC suggest that they influence different molecular signaling mechanisms within common target progenitor cells.