Heppner F L, Roth K, Nitsch R, Hailer N P
Department of Cell and Neurobiology, Institute of Anatomy, Humboldt University Hospital, Berlin, Germany.
Glia. 1998 Feb;22(2):180-8.
Microglial cells in the healthy adult CNS possess a characteristic ramified morphology and show little or no expression of major histocompatibility complex (MHC) or adhesion molecules. In contrast, microglial cells isolated from newborn rat brains inevitably show a nonramified amoeboid morphology and express immunoeffector molecules, such as MHC class I and II, and various adhesion molecules thought to be markers of microglial activation. Furthermore, they produce large amounts of oxygen radicals. Treatment of cultured microglial cells with the antioxidants vitamin E (alpha-tocopherol) and vitamin C (ascorbic acid) induced a ramified microglial morphology after 48 h in vitro, otherwise only seen in healthy adult CNS tissue or in co-culture with astrocytes. Morphological transformation of microglial cells was quantified by morphometric analysis and was found to be statistically significant. Ramification of microglia induced by vitamin E was accompanied by downregulated expression of adhesion molecules leukocyte function antigen-1, very late antigen-4, and intercellular adhesion molecule-1, as assessed by FACS analysis and immunocytochemistry. Moreover, cell numbers of microglia treated with vitamin E remained stable within 7 days in vitro, whereas untreated controls showed a cell loss of 81.5%. These data show that vitamin E acts as a protective compound in dissociated microglial cell cultures. In conclusion, our results suggest that vitamin E and vitamin C shift microglial morphology toward ramification and induce an immunological deactivation. These changes seem to be mediated by oxidative mechanisms.
健康成年中枢神经系统中的小胶质细胞具有典型的分支状形态，主要组织相容性复合体（MHC）或黏附分子的表达很少或没有表达。相比之下，从新生大鼠脑中分离出的小胶质细胞不可避免地呈现出非分支状的阿米巴样形态，并表达免疫效应分子，如MHC I类和II类，以及各种被认为是小胶质细胞活化标志物的黏附分子。此外，它们会产生大量的氧自由基。在体外培养48小时后，用抗氧化剂维生素E（α-生育酚）和维生素C（抗坏血酸）处理培养的小胶质细胞，可诱导出分支状的小胶质细胞形态，否则这种形态仅见于健康成年中枢神经系统组织或与星形胶质细胞共培养时。通过形态计量分析对小胶质细胞的形态转化进行量化，发现具有统计学意义。通过荧光激活细胞分选分析和免疫细胞化学评估，维生素E诱导的小胶质细胞分支伴随着黏附分子白细胞功能抗原-1、极晚期抗原-4和细胞间黏附分子-1表达的下调。此外，用维生素E处理的小胶质细胞在体外7天内细胞数量保持稳定，而未处理的对照组细胞损失了81.5%。这些数据表明，维生素E在解离的小胶质细胞培养物中起保护作用。总之，我们的结果表明，维生素E和维生素C使小胶质细胞形态向分支状转变，并诱导免疫失活。这些变化似乎是由氧化机制介导的。
