Lee S C, Liu W, Roth P, Dickson D W, Berman J W, Brosnan C F
Department of Pathology (Neuropathology), Albert Einstein College of Medicine, Bronx, NY 10461.
J Immunol. 1993 Jan 15;150(2):594-604.
CSF-1 is a growth factor that selectively promotes the proliferation, survival, and differentiation of cells of the mononuclear phagocyte series. As part of a study on the role of cytokine and hematopoietic growth factors in central nervous system (CNS) development and inflammation, we examined the expression of CSF-1 in dissociated glial cells cultured from human fetal CNS tissue. CSF-1 mRNA and protein were constitutively expressed by astrocytes. The steady state level of CSF-1 mRNA was markedly up-regulated by both IL-1 beta and TNF-alpha in a time- and dose-dependent manner, whereas only a minimal increase was detected after stimulation with LPS. In unstimulated astrocyte cultures, CSF-1 protein levels gradually increased to 3.5-fold base-line values by 96 h and were significantly increased by all three stimulants in the order of IL-1 > or = TNF > LPS. Low levels of CSF-1 mRNA and protein were also detected in unstimulated microglia cultures. In contrast to astrocyte cultures, CSF-1 mRNA and protein increased significantly after stimulation with LPS, but changed only minimally after exposure to TNF-alpha or IL-1 beta. The effect of CSF-1 on cell proliferation, morphology, and class II MHC Ag expression was determined in highly enriched cultures of microglia and astrocytes. Microglia treated with CSF-1 showed a modest level of proliferation and differentiation into rod-shaped cells, whereas neither cell number nor shape was changed in astrocyte cultures. Interestingly, marked inhibition of both basal and IFN gamma-induced class II MHC Ag expression was observed in microglial cells cultured in the presence of CSF-1, whereas no effect was detected in astrocytes. These results suggest the possibility that in situ production of CSF-1 in the CNS may regulate normal glial cell development and contribute to the immunologic status of the CNS through the down-regulation of class II MHC expression.
集落刺激因子-1（CSF-1）是一种生长因子，可选择性地促进单核吞噬细胞系列细胞的增殖、存活和分化。作为关于细胞因子和造血生长因子在中枢神经系统（CNS）发育及炎症中作用的研究的一部分，我们检测了从人胎儿CNS组织培养的解离神经胶质细胞中CSF-1的表达。星形胶质细胞组成性表达CSF-1 mRNA和蛋白。IL-1β和TNF-α均以时间和剂量依赖性方式显著上调CSF-1 mRNA的稳态水平，而用脂多糖（LPS）刺激后仅检测到最小程度的增加。在未刺激的星形胶质细胞培养物中，CSF-1蛋白水平在96小时时逐渐增加至基线值的3.5倍，并且三种刺激物均使其显著增加，增加幅度顺序为IL-1≥TNF＞LPS。在未刺激的小胶质细胞培养物中也检测到低水平的CSF-1 mRNA和蛋白。与星形胶质细胞培养物相反，LPS刺激后CSF-1 mRNA和蛋白显著增加，但暴露于TNF-α或IL-1β后变化很小。在高度富集的小胶质细胞和星形胶质细胞培养物中测定了CSF-1对细胞增殖、形态和II类主要组织相容性复合体（MHC）抗原表达的影响。用CSF-1处理的小胶质细胞显示出适度的增殖并分化为杆状细胞，而星形胶质细胞培养物中的细胞数量和形状均未改变。有趣的是，在存在CSF-1的情况下培养的小胶质细胞中观察到对基础和干扰素γ诱导的II类MHC抗原表达均有明显抑制，而在星形胶质细胞中未检测到影响。这些结果提示，CNS中CSF-1的原位产生可能调节神经胶质细胞的正常发育，并通过下调II类MHC表达对CNS的免疫状态产生影响。
