Direct Comparison of the Effects of CSF-1 (M-CSF) and GM-CSF on Human Monocyte DNA Synthesis and CSF Receptor Expression

There is evidence that a proportion of human monocytes can proliferate in vitro in response to colony-stimulating factor-1 (CSF-1, also known as M-CSF) and granulocyte-macrophage CSF (GM-CSF). To determine whether there are differences in DNA synthesis responses to these CSF, a large study using purified human peripheral blood monocytes from 45 donors was performed under optimized culture conditions. In contrast to the consistent response to CSF-1, approximately 20% of donors have monocytes that do not respond or have a minimal DNA synthesis response to GM-CSF stimulation. However, analysis demonstrated that no statistically significant differences exist in the levels of CSF-1 and GM-CSF-stimulated proliferation in monocytes. In addition, CSF-1 receptor (CSF-1R) blocking experiments indicated that a proportion of the GM-CSF-induced DNA synthesis is due to endogenous levels of CSF-1. As a further comparison of the actions of the two CSFs, CSF-1R and GM-CSFR levels were measured by flow cytometry, and it was shown that GM-CSFR levels decreased within 5 days of culture, independent of the conditions examined. In contrast, CSF1R levels at day 5 approximated those measured in uncultured monocytes. Whether the proliferating subpopulation(s) express one or both CSF receptors at the beginning or at the end of culture is as yet unknown. The information obtained in this study will be useful for the design of strategies to enrich for the subpopulation in question based on CSF receptor expression.