Survival of mononuclear phagocytes depends on a lineage-specific growth factor that the differentiated cells selectively destroy.
CSF-1 is a hemopoietic growth factor that specifically causes the proliferation and differentiation of mononuclear phagocytic cells. Receptors for CSF-1 occur exclusively on cells of the mononuclear phagocytic series (precursor leads to monoblast leads to promonocyte leads to monocyte leads to macrophage). Studies of the actions of CSF-1 on freshly explanted macrophages have been complicated by contamination of the primary cell isolates with CSF-1-producing cells and by the heterogeneity of the proliferative responses of individual macrophages. A method is described for the production of a highly purified and homogeneous population of adherent bone marrow-derived macrophages (BMMs) that are devoid of CSF-1-producing cells. The method may also be used to obtain nonadherent precursors of the mononuclear phagocytic series. Studies of CSF-1 action and degradation in cultures of BMMs have revealed several new findings. First, CSF-1 is required for both the survival (without proliferation) and the proliferation of BMMs. Second, CSF-1 is degraded by BMMs in a concentration-dependent manner, over the range of concentrations that stimulates both cell survival and proliferation. Third, the rate of CSF-1 degradation is saturable (or approximately 7 X 10(4) molecules per cell per hour) at CSF-1 concentrations that cause maximum proliferation (or approximately 0.4 nM). Under these conditions, BMMs are greatly enlarged and contain numerous phase-lucent vacuoles. Thus macrophages specifically require CSF-1 for both survival and proliferation, yet selectively and rapidly degrade it. This apparent dichotomy may have important implications for the role of CSF-1 in macrophage homeostasis in vivo.
D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002469:Cell Separation / Q000379:methods; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006410:Hematopoiesis / Q000187:drug effects; D008264:Macrophages / Q000502:physiology*; D051379:Mice
D003115:Colony-Stimulating Factors