Peripheral administration of lipopolysaccharide induces activation of microglial cells in rat brain
Peripheral administration of lipopolysaccharide induces activation of microglial cells in rat brain
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DOI：
10.1016/0197-0186(95)00141-7
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发表时间：
1996-07-01
影响因子：
4.2
通讯作者：
Boddeke, HWGM
中科院分区：
文献类型：
--
作者：
Buttini, M;Limonta, S;Boddeke, HWGM
应用抗表面免疫分子单克隆抗体免疫细胞化学和Griffonia simplicifolia凝集素组织化学方法，观察了静脉注射脂多糖（LPS）后大鼠脑内小胶质细胞的反应。在给予1、2.5和5 mg/kg LPS后数小时内，整个脑中的小胶质细胞活化变得明显，并在8-24 h达到峰值。高剂量的LPS（2.5和5毫克/公斤）诱导的形态过渡的休息分支小胶质细胞的圆形，巨噬细胞样细胞在前下丘脑，丘脑和脑干。注射1 mg/kg LPS后，仅在脑干中检测到这种形态学转变。LPS给药后7天内，小胶质细胞反应性逐渐恢复至对照水平。此外，LPS诱导的小胶质细胞的MHC II类的表达增强。注射LPS后3天，发现MHC II类Ia抗原的最大上调，并且在注射LPS后7天仅检测到少数高度Ia免疫反应性细胞。尽管在大鼠脑中存在高度活化的小胶质细胞，但在注射LPS后的任何时间点均未观察到组织损伤的迹象。除了小胶质细胞的激活外，静脉注射LPS还诱导脉络丛和大脑血管中巨噬细胞的积聚，但没有检测到血管破裂以及随后血巨噬细胞侵入实质。我们的数据表明，外周免疫攻击导致大脑中小胶质细胞的高度和短暂激活，这可能有助于感染和感染性休克的病理学。版权所有（C）1996 Elsevier Science Ltd.
Using immunocytochemistry with monoclonal antibodies against surface immunomolecules and Griffonia simplicifolia lectin histochemistry, the microglial cell reaction in rat brain was studied after intravenous injection of lipopolysaccharide (LPS). Activation of microglial cells throughout the brain became apparent within hours and peaked at 8-24 h following administration of 1, 2.5 and 5 mg/kg LPS. High doses of LPS (2.5 and 5 mg/kg) induced a morphological transition of resting ramified microglia to round, macrophage-like cells in the anterior hypothalamus, thalamus and the brainstem. After injection of 1 mg/kg LPS, this morphological transition was only detected in the brainstem. Microglial cell reactivity gradually returned to control levels within 7 days after LPS administration. Furthermore, LPS induced enhanced expression of MHC class II by microglial cells. Maximal up-regulation of MHC class II Ia-antigen was found 3 days following injection of LPS, and only a few highly Ia immunoreactive cells were detectable 7 days following injection of LPS. Despite the presence of highly activated microglial cells in the rat brain, no signs of tissue damage were observed at any time point after injection of LPS examined. In addition to the activation of microglial cells, intravenous injection of LPS induced accumulations of macrophages in blood vessels of the choroid plexus and the brain, but no disruption of vessels with subsequent invasion of parenchyma by blood macrophages was detected. Our data demonstrate that a peripheral immune challenge leads to a high and transitory activation of microglial cells in the brain which could possibly contribute to the pathology of infections and septic shock. Copyright (C) 1996 Elsevier Science Ltd.