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 → monoblast → promonocyte → monocyte → 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 (∼7 × 104 molecules per cell per hour) at CSF-1 concentrations that cause maximum proliferation (∼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.