title: Bone marrow-derived macrophages: development and regulation of differentiation markers by colony-stimulating factor and interferons.
abstract: To investigate the role of specific cytokines in the development of the fully mature macrophage, we have employed murine bone marrow cells that were grown in the presence of CSF-1, a colony-stimulating factor that has been shown to induce the proliferation and differentiation of macrophages from their precursor cells. The CSF-1 employed in these studies was partially purified to ensure removal of contaminating interferon (IFN) from the preparations. After 1 to 2 wk in the presence of the partially purified CSF-1, the adherent macrophages were removed from flasks enzymatically and were recultured at known densities in the absence of CSF-1. Cell surface antigens (Mac-1 and Ia) and Fc receptor capacity (as assessed by Fc-mediated phagocytosis) were examined as markers of macrophage differentiation. Basal levels of Fc receptor capacity and Mac-1 antigen were markedly influenced by exposure to CSF-1, and appear to be modulated by CSF-induced, macrophage-derived IFN. When the bone marrow-derived macrophages were exposed to exogenous IFN in the absence of CSF-1, they proved to be extremely inducible with respect to Fc-mediated phagocytosis (IFN-beta and rIFN-gamma) and Ia antigen expression (rIFN-gamma) when compared with thioglycollate-elicited macrophages. Thus, macrophage growth factors, such as CSF-1, promote macrophage maturation by inducing the production of autostimulatory signals, such as macrophage-derived IFN. In addition, exogenous cytokine stimuli, such as IFN-gamma, further amplify the differentiative potential of these cells. Bone marrow-derived macrophages, propagated under well-defined conditions and never exposed to eliciting agents, provide a powerful model for studying the role of cytokines, such as CSF-1 and IFN, in the differentiative pathway of macrophages.
authors.forename: M K
authors.initials: MK
authors.lastname: Warren
authors.forename: S N
authors.initials: SN
authors.lastname: Vogel
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007372:Interferons / Q000494:pharmacology*; D016177:Macrophage-1 Antigen; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D010587:Phagocytosis; D011961:Receptors, Fc / Q000032:analysis / Q000502:physiology
chemical_list: D000954:Antigens, Surface; D003115:Colony-Stimulating Factors; D000949:Histocompatibility Antigens Class II; D016177:Macrophage-1 Antigen; D011961:Receptors, Fc; D007372:Interferons