Postler E, Lehr A, Schluesener H, Meyermann R
Institute of Brain Research, University of Tübingen, Germany.
Glia. 1997 Jan;19(1):27-34. doi: 10.1002/(sici)1098-1136(199701)19:1<27::aid-glia3>3.0.co;2-7.
So far, microglial activation in cerebral ischemia has only been studied in different animal models. We have investigated the activation of microglial cells in human cerebral ischemia. As a marker for the activation of these "brain macrophages," we have used the macrophage inhibitor factor-related-proteins MRP-8 and MRP-14, which belong to the calcium binding S-100 protein family. The proteins can be detected on microglial cells in bacterial encephalitis and Alzheimer's disease but have so far not been studied in non-inflammatory diseases, in which microglial activation also occurs. Antibodies against MRP-8 and -14 detected ramified microglial cells within the first 3 days after cerebral infarction. Labeled cells were found selectively in the periinfarctional area. To support the notion that these cells belong to the locally activated resident microglial population, we studied their proliferation rate by staining the Ki-67 antigen with the antibody MIB-1. Double-labeling clearly showed that in the early phase of cerebral infarction microglial cells in the periinfarctional area express MRP-8 and -14 and also proliferate. Surprisingly, MRPs are expressed no longer than 3 days post infarction. This indicates that the activation of the resident microglia is an early step of tissue reaction after cerebral infarction. Additionally, we found evidence that microglial cells contribute to the population of phagocytes only during the first 3 days post infarction. The majority of lipid phagocytes found in the later stages are obviously recruited from the blood-borne macrophage pool.
到目前为止，脑缺血中微胶质细胞的激活仅在不同动物模型中进行了研究。我们对人脑缺血中微胶质细胞的激活进行了调查。作为这些“脑巨噬细胞”激活的标志物，我们使用了巨噬细胞抑制因子相关蛋白MRP - 8和MRP - 14，它们属于钙结合S - 100蛋白家族。在细菌性脑炎和阿尔茨海默病的微胶质细胞上可以检测到这些蛋白，但迄今为止尚未在也会发生微胶质细胞激活的非炎症性疾病中进行研究。针对MRP - 8和 - 14的抗体在脑梗死发生后的头3天内检测到了分支状的微胶质细胞。标记细胞选择性地出现在梗死周边区域。为了支持这些细胞属于局部激活的常驻微胶质细胞群体这一观点，我们通过用抗体MIB - 1对Ki - 67抗原进行染色来研究它们的增殖率。双重标记清楚地表明，在脑梗死的早期阶段，梗死周边区域的微胶质细胞表达MRP - 8和 - 14并且也会增殖。令人惊讶的是，MRP在梗死后3天内就不再表达。这表明常驻小胶质细胞的激活是脑梗死组织反应的早期步骤。此外，我们发现有证据表明，微胶质细胞仅在梗死后的头3天内对吞噬细胞群体有贡献。在后期发现的大多数脂质吞噬细胞显然是从血源巨噬细胞库中招募来的。
