Human monocyte-derived dendritic cells produce macrophage colony-stimulating factor: enhancement of c-fms expression by interleukin-10.
Human monocyte-derived dendritic cells (DC) generated with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4 express c-fms (CD115), the receptor for macrophage-CSF (M-CSF). Expression of c-fms on monocyte-derived DC has been interpreted as the susceptibility of these cells to M-CSF-induced macrophage development. We show here that homogeneous cultures of CD14 DC constitutively produced large amounts of M-CSF. However, presence of M-CSF neither induced macrophage development nor did it prevent terminal maturation into CD83+ DC. M-CSF production by DC was driven by GM-CSF and inhibited by the specific phosphatidylinositol 3-kinase inhibitor wortmannin. M-CSF synthesis was rapidly induced during the first 24 h of DC culture and then declined during the 5-day culture period. Replating of the cells, which was associated by a transient adherence, always induced a strong up-regulation of M-CSF synthesis. Addition of recombinant IL-10 to DC cultures enhanced c-fms expression and induced macrophage development as measured by the strong up-regulation of CD14 expression as well as by enhanced expression of the Fcgamma receptors I, II, and III (CD64, CD32, CD16). Our data demonstrate that immature monocyte-derived DC produce M-CSF which does not induce macrophage development, despite the surface expression of c-fms on DC. IL-10 appears to induce macrophage development by up-regulating c-fms and, thereby, enhancing the sensitivity of the cells to endogenously produced M-CSF.
Department of Urology, University of Innsbruck, Austria.
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Rieser
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Ramoner
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Böck
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Deo
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Höltl
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Bartsch
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Thurnher
D000730:Androstadienes / Q000494:pharmacology; D000954:Antigens, Surface / Q000378:metabolism; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology*; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D000077191:Wortmannin
D000730:Androstadienes; D000954:Antigens, Surface; D017931:DNA Primers; D004791:Enzyme Inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012333:RNA, Messenger; D016753:Interleukin-10; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor; D000077191:Wortmannin