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 (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.
Panterne
B
B
Laboratoire de Biologie Cellulaire et Moléculaire des Factueurs de Croissance, C.N.R.S., UPR 272, 94800 Villejuif, France.
Zhou
Y Q
YQ
Hatzfeld
J
J
Li
M L
ML
Levesque
J P
JP
Clark
S C
SC
Hatzfeld
A
A
D001853:Bone Marrow / Q000378:metabolism*; D001854:Bone Marrow Cells; D002452:Cell Count; D016922:Cellular Senescence; D015536:Down-Regulation; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D016173:Macrophage Colony-Stimulating Factor / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D012016:Reference Values; D013234:Stem Cells / Q000378:metabolism*
D012333:RNA, Messenger; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor