SURVIVAL OF MONONUCLEAR PHAGOCYTES DEPENDS ON A LINEAGE-SPECIFIC GROWTH-FACTOR THAT THE DIFFERENTIATED CELLS SELECTIVELY DESTROY
SURVIVAL OF MONONUCLEAR PHAGOCYTES DEPENDS ON A LINEAGE-SPECIFIC GROWTH-FACTOR THAT THE DIFFERENTIATED CELLS SELECTIVELY DESTROY
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DOI:
10.1016/0092-8674(82)90376-2
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发表时间:
1982-01-01
期刊:
影响因子:
64.5
通讯作者:
STANLEY, ER
中科院分区:
文献类型:
--
作者:
TUSHINSKI, RJ;OLIVER, IT;STANLEY, ER
CSF-1 (colony stimulating factor-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 .fwdarw. monoblast .fwdarw. promonocyte .fwdarw. monocyte .fwdarw. 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 (mouse) bone marrow-derived macrophages (BMM) 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 BMM have revealed several new findings. CSF-1 is required for both the survival (without proliferation) and the proliferation of BMM. CSF-1 is degraded by BMM in a concentration-dependent manner, over the range of concentrations that stimulates both cell survival and proliferation. The rate of CSF-1 degradation is saturable (.apprx. 7 .times. 104 molecules/cell per hour) at CSF-1 concentrations that cause maximum proliferation (.apprx. 0.4 nM). Under these conditions, BMM 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.