Staining of HLA-DR, Ibal and CD68 in human microglia reveals partially overlapping expression depending on cellular morphology and pathology
Staining of HLA-DR, Ibal and CD68 in human microglia reveals partially overlapping expression depending on cellular morphology and pathology
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DOI：
10.1016/j.jneuroim.2017.04.007
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发表时间：
2017-08-15
影响因子：
3.3
通讯作者：
Huitinga, Inge
中科院分区：
文献类型：
--
作者：
Hendrickx, Debbie A. E.;van Eden, Corbert G.;Huitinga, Inge
HLA-DR、IBAL和CD68是人类组织中广泛使用的小胶质细胞标志物。然而，由于基因调控的不同，他们可能会识别不同的小胶质细胞激活阶段。在这里，我们直接比较了不同表型的小胶质细胞，从分枝状到阿米巴样细胞，到泡沫吞噬巨噬细胞，在相邻切片中两种标志物的免疫细胞化学双重染色的HLA-DR、IBAL和CD68的表达。材料来自被诊断为多发性硬化症(MS)和阿尔茨海默病(AD)的患者和对照组，因为它们一起包含了急性和慢性炎症环境中的所有小胶质细胞激活阶段。我们发现了一个相似但不完全相同的整体表达模式。3种标志物均由慢性活动期MS病变周围的分支/阿米巴样小胶质细胞表达，但HLADR与IBALL之间的重叠有限。MS活动期病变脱髓鞘边缘的泡沫状巨噬细胞表达FILA-DR和CD68的水平高于IBALL。所有标记物均以MS NAWM中的小胶质细胞堆积(结节)表达。海马区致密的AD核心斑块主要与表达HLA-DR的小胶质细胞有关。弥漫性AD斑块与小胶质细胞无关。这些结果表明，小胶质细胞标志物在神经病理学分析中具有不同的潜力，其中HLA-DR和CD68反映了免疫激活和对组织损伤的反应，IBALL提供了一种更适合于在没有病理学的情况下进行结构研究的标志物。
HLA-DR, Ibal and CD68 are widely used microglia markers in human tissue. However, due to differences in gene regulation, they may identify different activation stages of microglia. Here, we directly compared the expression of HLA-DR, Ibal and CD68 in microglia with different phenotypes, ranging from ramified to amoeboid, to foamy phagocytizing macrophages, in adjacent sections immunocytochemically double stained for two of the markers. Material was used from patients diagnosed with multiple sclerosis (MS) and Alzheimer's disease (AD) patients and control subjects because together they contain all the microglia activation stages in an acute and a chronic inflammatory setting. We found a similar, yet not identical, overall expression pattern. All three markers were expressed by ramified/amoeboid microglia around chronic active MS lesions, but overlap between HLA-DR and Ibal was limited. Foamy macrophages in the demyelinating rims of active MS lesions of MS expressed more FILA-DR and CD68 than Ibal. All markers were expressed by small microglia accumulations (nodules) in MS NAWM. Dense core AD plaques in the hippocampus were mostly associated with microglia expressing HLA-DR. Diffuse AD plaques were not specifically associated with microglia at all. These results indicate that microglia markers have different potential for neuropathological analysis, with HLA-DR and CD68 reflecting immune activation and response to tissue damage, and Ibal providing a marker more suited for structural studies in the absence of pathology.