Dynamics of microglial activation after human traumatic brain injury are revealed by delayed expression of macrophage-related proteins MRP8 and MRP14
Dynamics of microglial activation after human traumatic brain injury are revealed by delayed expression of macrophage-related proteins MRP8 and MRP14
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DOI：
10.1007/s004019900172
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发表时间：
2000-09-01
影响因子：
12.7
通讯作者：
Meyermann, R
中科院分区：
文献类型：
--
作者：
Engel, S;Schluesener, H;Meyermann, R
人类创伤性脑损伤（TBI）是研究人类小胶质细胞激活动力学的理想选择，因为损伤形成的开始是精确定义的。目前的研究提供了巨噬细胞/小胶质细胞反应明显延迟的证据。对18例脑外伤存活1 ~ 6个月的患者进行免疫组织学分析。使用针对小胶质细胞/巨噬细胞抗原(主要组织相容性复合体II类、CD4、白细胞介素（IL)-16、巨噬细胞相关蛋白（MRP） 8和MRP14）的抗体，研究挫伤区和非挫伤区样本。IL-16是CD4的一种天然配体，在所有病例中，在整个大脑中有许多小胶质细胞组成性地表达。血管周围细胞有规律地检测到CD4。MRP8和MRP14仅在活化的巨噬细胞和小胶质细胞上表达，仅在TBI后存活时间超过72小时的脑内检测到。此外，通过MIB-1检测到的小胶质细胞增殖直到72小时才出现。这种延迟表达的激活标记物MRP8和MRP14以及增殖标记物MIB-1与实验性闭闭性脑损伤相当，但与缺血性脑的急性激活有严格区别。
Human traumatic brain injury (TBI) is ideally suited for investigation of the kinetics of human microglial cell activation as the onset of lesion formation is precisely defined. The present study provides evidence of a distinct delay in macrophage/microglia response following TBI. Eighteen brains of patients who had survived TBI for 1 h to 6 months were analysed by immunohistology. Samples of contusional and non-contusional areas were studied using antibodies directed against antigens of microglia/macrophages [major histocompatibility complex class II, CD4, interleukin (IL)-16, macrophage-related protein (MRP) 8 and MRP14]. IL-16, a natural ligand to CD4, was expressed constitutively by numerous microglial cells in all cases throughout the brain. CD4 could be detected regularly on perivascular cells. MRP8 and MRP14, which are only expressed on activated macrophages and microglial cells, could be detected only within brains with a survival time of more than 72 h post TBI. In addition, proliferation of microglia detected by MIB-1 was not present until 72 h. This delayed expression of the activation markers MRP8 and MRP14 and the proliferation marker MIB-1 is comparable to experimental closed head injuries but strictly different from acute activation found in ischemic brains.