Production of monocyte chemotactic protein-1 by rat brain macrophages
Production of monocyte chemotactic protein-1 by rat brain macrophages
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DOI：
10.1111/j.1460-9568.1996.tb01316.x
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发表时间：
1996-08-01
影响因子：
3.4
通讯作者：
Mallat, M
中科院分区：
文献类型：
--
作者：
Calvo, CF;Yoshimura, T;Mallat, M
在本研究中，我们表明，培养的大鼠脑巨噬细胞释放的可溶性因子，刺激骨髓来源的巨噬细胞的迁移，在体外趋化性测定确定。棋盘格分析表明，大部分的这种效果是由于极化迁移的细胞（趋化现象），而不是在增加细胞运动（趋化）。针对大鼠单核细胞趋化蛋白-1（趋化因子MCP-1）的免疫血清显着降低了这种活性。北方印迹分析表明MCP-1基因在培养的脑巨噬细胞中表达，但在未刺激的骨髓源性巨噬细胞中不表达。MCP-1的表达上调时，观察到脂多糖被添加到培养的脑巨噬细胞，刺激6小时后出现一个高峰。此外，炎性细胞因子如白细胞介素（II）-1 β，集落刺激因子-1，肿瘤坏死因子-α和IL-6单独增加MCP-1 mRNA的基础水平。随后，我们证明了MCP-1在成年大鼠脑损伤后局部注射红藻氨酸诱导的体内生产。MCP-1的合成定位于星形胶质细胞和脑巨噬细胞。这些结果表明，静息小胶质细胞活化为脑巨噬细胞及其随后分泌的趋化因子可能有助于该机制，导致血液来源的单核细胞浸润CNS，如在几种病理学中观察到的。
In the present study, we show that cultured rat brain macrophages release a soluble factor that stimulates the migration of bone marrow-derived macrophages, as determined by an in vitro chemotaxis assay. A checkerboard analysis indicated that most of this effect resulted from a polarized migration of the cells (chemotactic phenomenon), rather than in an increase in cell motility (chemokinesis). This activity was significantly decreased by an immune serum directed against the rat monocyte chemoattractant protein-1 (chemokine MCP-1). Northern blot analysis demonstrated expression of the MCP-1 gene in cultured brain macrophages, but its absence in unstimulated bone marrow-derived macrophages. Up-regulation of MCP-1 expression was observed when lipopolysaccharide was added to cultured brain macrophages, a peak occurring after a 6 h period of stimulation. Also, inflammatory cytokines such as interleukin (II)-1 beta, colony stimulating factor-1, tumour necrosis factor-alpha and IL-6 individually increased the basal level of MCP-1 mRNA. Subsequently, we demonstrated the in vivo production of MCP-1 in the adult rat brain following injury induced by a local injection of kainic acid. MCP-1 synthesis was localized in both astrocytes and brain macrophages. These results suggest that the activation of resting microglial cells into brain macrophages and their subsequent secretion of chemokines could contribute to the mechanism(s), leading to the infiltration of the CNS by blood-derived monocytes, as observed in several pathologies.