CSF-1 CONTROL OF C-FMS EXPRESSION IN NORMAL HUMAN BONE-MARROW PROGENITORS

We have previously shown (Zhou et al: Blood, 72:1870, 1988) that IL3, added with low concentrations of CSF-1 (I ng/ml) to normal human CD34 enriched cells, promoted the development of various types of colonies including those containing immature monocytes. However, when high con centrations 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+ cell s, of a subpopulation of immature progenitors which express the CSF-1 receptor (c-fms) mRNA. The expression of c-FMS protein was also substa ntiated by immunocytochemical studies using anti-c-fms antibody. The p ercentage of c-fms positive cells peaked at day 7 and began to decreas e 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 monoc ytes or progenitors of monocytes and that CSF-1 modulates c-fms expres sion. 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-regul ation of c-fms mRNA and protein was seen. No down-regulation was obser ved with low concentration of CSF-1 (1 ng/ml). The possibility that di fferent concentrations of CSF-1 could modulate the development of mono cytic progenitors is discussed.