1,25-Dihydroxyvitamin D3 modulates colony-stimulating factor-1 receptor binding by murine bone marrow macrophage precursors.
1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] has been shown to be a potent agent for monocyte/macrophage differentiation in leukemic cell lines. This study examines the differentiational effects of 1,25-(OH)2D3 in authentic murine bone marrow immature uncommitted precursor cells collected by pretreatment of murine bone marrow with 5-fluorouracil (5-FU). Early precursor cells, collected 1 day after 5-FU treatment, are characterized by low expression of the colony-stimulating factor-1. (CSF-1) receptor and dependence on both CSF-1 and interleukin-1 for growth. Intermediate precursors were collected 5 days after 5-FU treatment and required either CSF-1 or interleukin-3 for growth. Intermediate precursors expressed relatively higher levels of the CSF-1 receptor. Addition of 1,25-(OH)2D3 to these populations inhibited proliferation, as measured by [3H]thymidine incorporation and soft agar colony assay. Furthermore, 1,25-(OH)2D3 caused a more rapid appearance of the CSF-1 receptor in early precursor cells in a dose-dependent metabolite-specific manner. Conversely, CSF-1 receptor expression was decreased in intermediate precursors treated with the steroid. This decrease in receptor expression was also dose dependent and metabolite specific. These findings demonstrate that 1,25-(OH)2D3 1) targets to authentic bone marrow macrophages at various stages of differentiation and 2) modulates expression of the CSF-1 receptor, a protein which, in turn, regulates monocytic maturation.
Perkins
S L
SL
Department of Pathology, Jewish Hospital, Washington University Medical Center, St. Louis, Missouri 63110.
Teitelbaum
S L
SL
D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004261:DNA Replication / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007375:Interleukin-1 / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism* / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000187:drug effects / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism
D007375:Interleukin-1; D007377:Interleukin-3; D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor; D002117:Calcitriol; D013936:Thymidine