Hendrickx Debbie A E, van Eden Corbert G, Schuurman Karianne G, Hamann Jörg, Huitinga Inge
Neuroimmunology Research Group, Netherlands Institute for Neuroscience, Meibergdreef 47, 1105 BA Amsterdam, The Netherlands.
Neuroimmunology Research Group, Netherlands Institute for Neuroscience, Meibergdreef 47, 1105 BA Amsterdam, The Netherlands; Department of Experimental Immunology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
J Neuroimmunol. 2017 Aug 15;309:12-22. doi: 10.1016/j.jneuroim.2017.04.007. Epub 2017 Apr 20.
HLA-DR, Iba1 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, Iba1 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 Iba1 was limited. Foamy macrophages in the demyelinating rims of active MS lesions of MS expressed more HLA-DR and CD68 than Iba1. 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 Iba1 providing a marker more suited for structural studies in the absence of pathology.
HLA - DR、Iba1和CD68是人类组织中广泛使用的小胶质细胞标志物。然而，由于基因调控的差异，它们可能识别小胶质细胞的不同激活阶段。在这里，我们通过对相邻切片进行两种标志物的免疫细胞化学双重染色，直接比较了HLA - DR、Iba1和CD68在从分支状到阿米巴样再到泡沫状吞噬巨噬细胞等不同表型的小胶质细胞中的表达。材料取自被诊断患有多发性硬化症（MS）的患者、阿尔茨海默病（AD）患者和对照受试者，因为他们共同包含了急性和慢性炎症环境下所有的小胶质细胞激活阶段。我们发现了一种相似但不完全相同的总体表达模式。所有这三种标志物都在慢性活动性MS病变周围的分支状/阿米巴样小胶质细胞中表达，但HLA - DR和Iba1之间的重叠有限。MS活动性病变脱髓鞘边缘的泡沫状巨噬细胞表达的HLA - DR和CD68比Iba1更多。所有标志物都在MS正常脑白质中的小胶质细胞小聚集物（结节）中表达。海马体中的致密核心AD斑块大多与表达HLA - DR的小胶质细胞相关。弥漫性AD斑块根本与小胶质细胞没有特异性关联。这些结果表明，小胶质细胞标志物在神经病理学分析中有不同的潜力，HLA - DR和CD68反映免疫激活和对组织损伤的反应，而Iba1在无病理学情况下提供了一个更适合结构研究的标志物。
