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
STANLEY, ER
中科院分区:
生物学1区
文献类型:
--
作者:
TUSHINSKI, RJ;OLIVER, IT;STANLEY, ER

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CSF-1(集落刺激因子-1)是一种造血生长因子,特异性地引起单核吞噬细胞的增殖和分化。CSF-1的受体仅出现在单核吞噬细胞系列的细胞上(前体→单核细胞前单核细胞→单核细胞→巨噬细胞)。CSF-1对新鲜培养的巨噬细胞的作用的研究已经被CSF-1产生细胞的原代细胞分离物的污染和单个巨噬细胞的增殖反应的异质性所复杂化。描述了一种用于生产高度纯化且均质的贴壁(小鼠)骨髓源性巨噬细胞(BMM)群体的方法,所述巨噬细胞缺乏产生CSF-1的细胞。该方法也可用于获得单核吞噬细胞系列的非粘附前体。CSF-1的行动和降解的研究文化的BMM揭示了几个新的发现。CSF-1对于BMM的存活(无增殖)和增殖都是必需的。在刺激细胞存活和增殖的浓度范围内,BMM以浓度依赖性方式降解CSF-1。CSF-1降解的速率是可饱和的(约7倍。104个分子/细胞/小时),在引起最大增殖的CSF-1浓度下(约104个分子/细胞/小时)。0.4 nM)。在这些条件下,BMM大大扩大,并含有许多相透明的液泡。因此,巨噬细胞特别需要CSF-1的生存和增殖,但选择性和快速降解it. This明显的二分法可能有重要意义的CSF-1在体内巨噬细胞稳态的作用。
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.