Differential and time-dependent expression of monocyte chemoattractant protein-1 mRNA by astrocytes and macrophages in rat brain: Effects of ischemia and peripheral lipopolysaccharide administration
Differential and time-dependent expression of monocyte chemoattractant protein-1 mRNA by astrocytes and macrophages in rat brain: Effects of ischemia and peripheral lipopolysaccharide administration
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DOI：
10.1016/s0165-5728(96)00203-2
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发表时间：
1997-04-01
影响因子：
3.3
通讯作者：
Boddeke, HWGM
中科院分区：
文献类型：
--
作者：
Gourmala, NG;Buttini, M;Boddeke, HWGM
越来越多的证据表明，在炎症过程中，趋化细胞因子在中枢神经系统（CNS）白细胞积聚中发挥着关键作用。单核细胞趋化蛋白 (MCP-1/JE) 是 β 趋化因子 (C-C 趋化因子) 家族的成员，可作为单核细胞的有效趋化剂和激活剂。我们使用原位杂交组织化学 (ISH) 研究了 MCP-1 mRNA 的诱导，并通过 ISH 和免疫细胞化学相结合，在缺血大鼠大脑以及内毒素处理的大鼠大脑中表征了其细胞来源。我们的结果表明，大脑中动脉闭塞（MCAO）后 6 小时至 2 天，MCP-1 mRNA 存在于缺血组织（半影）周围的星形胶质细胞中。在稍后的时间点（4 天后），在梗塞组织的巨噬细胞和反应性小胶质细胞中发现了 MCP-1 mRNA。外周施用细菌脂多糖（LPS）以时间依赖性方式（1小时至1天，表达峰值6-8小时）诱导整个大脑中MCP-1 mRNA的表达，并在星形胶质细胞中发现。总之，我们发现 MCP-1 在 (a) 星形胶质细胞中表达，在 MCA 闭塞后在巨噬细胞/反应性小胶质细胞中存在较小程度的表达，在 (b) 外周施用 LPS 后在星形胶质细胞中发现 MCP-1 表达。这些发现支持 MCP-1 参与中枢神经系统对急性创伤或感染的反应，因此可能在大脑炎症过程中发挥关键作用。
Increasing evidence indicates a key role of chemoattractant cytokines in the accumulation of leukocytes in the central nervous system (CNS) during the course of inflammatory processes. Monocyte chemoattractant protein (MCP-1/JE), a member of the beta-chemokine (C-C chemokine) family, functions as a potent chemoattractant and activator for monocytes. We have investigated the induction of MCP-1 mRNA using in situ hybridization histochemistry (ISH) and characterized its cellular source by combination of ISH and immunocytochemistry in ischemic rat brains as well as in brains of endotoxin-treated rats. Our results show that 6 h-2 d after middle cerebral artery occlusion (MCAO), MCP-1 mRNA is present in astrocytes surrounding the ischemic tissue (penumbra). At later time points (after 4 d), MCP-1 mRNA is found in macrophages and reactive microglia in the infarcted tissue. Peripheral administration of the bacterial lipopolysaccharide (LPS) induced MCP-1 mRNA throughout the brain in a time-dependent manner(1 h-1 d, peak of expression 6-8 h) and was found in astrocytes. In summary, we have found expression of MCP-1 in (a) astrocytes and to a lesser extent in macrophages/reactive microglia after MCA-occlusion and in (b) astrocytes after peripheral administration of LPS. These findings support that MCP-1 is involved in the CNS response to acute trauma or infection and thus may play a key role in inflammatory processes of the brain.