THE REGULATION OF MONONUCLEAR PHAGOCYTE ENTRY INTO S-PHASE BY THE COLONY STIMULATING FACTOR CSF-1

THE REGULATION OF MONONUCLEAR PHAGOCYTE ENTRY INTO S-PHASE BY THE COLONY STIMULATING FACTOR CSF-1
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DOI:
10.1002/jcp.1041220210
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发表时间:
1985-01-01
影响因子:
5.6
通讯作者:
STANLEY, ER
STANLEY, ER
中科院分区:
生物学2区
文献类型:
--
作者:
TUSHINSKI, RJ;STANLEY, ER

文献摘要

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CSF-1是一种造血生长因子,能特异性地调节[小鼠]单核吞噬细胞的存活、增殖和分化。采用不含脑脊液-1产生细胞的贴壁骨髓巨噬细胞群,研究脑脊液-1对巨噬细胞进入S时相的调节作用。95%以上的骨髓瘤细胞具有脑脊液-1受体。在体外培养条件下,93-98%的骨髓细胞处于周期状态(S时相8-9小时,倍增时间24-28小时)。BMM与15%的FCS共同孵育,在无CSF-1或有CSF-1浓度的情况下,诱导存活而不增殖,进入静止状态。这种状态的特点是DNA(98%)、总蛋白(35%)、核糖体蛋白(76%)和组蛋白(96%)的合成速度低于指数生长细胞中这些成分的合成速度。在骨髓基质细胞中加入脑脊液-1使之静止,因为去除脑脊液-1刺激进入S时相,滞后时间为.apprx。这一滞后期被缩短到8h,在浓度为CSF-1的静止期诱导存活而不增殖,这一效果可能与预期这些细胞的蛋白质含量更高有关。在滞后期的不同时间被抗体中和表明,任何细胞进入S时相几乎都需要整个滞后期的脑脊液-1。在去除血清和CSF1所致静止的骨髓瘤中,纯化的CSF1在无血清的情况下刺激细胞进入S期,而单独的血清则无效。这一结果与CSF-1在单核巨噬细胞增殖、存活和功能中的主要调节作用是一致的。
CSF-1 is a hemopoietic growth factor that specifically regulates the survival, proliferation, and differentiation of [mouse] mononuclear phagocytic cells. Populations of adherent bone marrow-derived macrophages (BMM) devoid of CSF-1 producing cells were used to study regulation by CSF-1 of macrophage entry into S phase. More than 95% of BMM possess the CSF-1 receptor. Of BMM 93-98% are cycling (S phase 8-9 h, doubling time 24-28 h) when cultured in the presence of CSF-1. BMM incubated with 15% FCS in the absence of CSF-1 or in the presence of CSF-1 concentrations inducing survival without proliferation enter a quiescent state. This state is characterized by a reduction in the synthesis of DNA (98%), total protein (35%), ribosomal protein (76%) and histone (96%) compared with the synthetic rate of these components in exponentially growing cells. Addition of CSF-1 to BMM rendered quiescent by removal of CSF-1 stimulated entry into S phase with a lag period of .apprx. 12 h. This lag period is reduced to 8 h in BMM made quiescent at concentrations of CSF-1 inducing survival without proliferation, an effect which may be related to the expected higher protein content of these cells. Neutralization of CSF-1 by antibody at different times during the lag period indicates that CSF-1 is required for almost the entire lag period for the entry of any cells into S phase. In BMM rendered quiescent by removal of both serum and CSF-1, purified CSF-1 without serum stimulated entry of cells into S phase, whereas serum alone was ineffective. The results are consistent with a primary regulatory role of CSF-1 in mononuclear phagocyte proliferation, survival and function.