CSF‐1 control of C‐FMS expression in normal human bone marrow progenitors

AbstractWe have previously shown (Zhou et al: Blood, 72:1870, 1988) that IL3, added with low concentrations of CSF‐1 (1 ng/ml) to normal human CD34+ enriched cells, promoted the development of various types of colonies including those containing immature monocytes. However, when high concentrations of CSF‐1 (20 ng/ml) were added alone or together with IL3, smaller colonies with mature macrophages were found. Here we show by in situ hybridization that IL3 allows the development, from CD34+ cells, of a subpopulation of immature progenitors which express the CSF‐1 receptor (c‐fms) mRNA. The expression of c‐FMS protein was also substantiated by immunocytochemical studies using anti‐c‐fms antibody. The percentage of c‐fms positive cells peaked at day 7 and began to decrease thereafter. When anti‐CSF‐1 antibodies were included in the culture, the decrease in c‐fms mRNA after day 7 was abrogated. This indicated that endogenous CSF‐1 was produced as CD34+ cells developed into monocytes or progenitors of monocytes and that CSF‐1 modulates c‐fms expression. We further demonstrated that when a high dose of CSF‐1 (20 ng/ml) was added at day 7 to IL3‐stimulated CD34+ cells, a rapid down‐regulation of c‐fms mRNA and protein was seen. No down‐regulation was observed with low concentration of CSF‐1 (1 ng/ml). The possibility that different concentrations of CSF‐1 could modulate the development of monocytic progenitors is discussed. © 1993 Wiley‐Liss, Inc.