Ilschner S, Brandt R
Institute of Neurobiology, University of Heidelberg, Germany.
Glia. 1996 Oct;18(2):129-40. doi: 10.1002/(SICI)1098-1136(199610)18:2<129::AID-GLIA5>3.0.CO;2-W.
In situ and in vitro, microglia can have different morphologies, which are thought to reflect distinct physiological activities. Two extreme forms are ameboid and ramified microglia. To study cytoskeletal changes during differentiation, we used defined cell culture systems to yield cultures of ameboid or ramified microglia from mouse brain. With respect to proliferation, secretion, receptor-expression, and phagocytosis, ramified microglia was generally less active. We found that the transition to a ramified phenotype was accompanied by an increase in the relative amount of acetylated and detyrosinated tubulin. Whereas the modified microtubules were restricted to regions close to the microtubule-organizing centers (MTOCs) in ameboid cells, acetylated microtubules were abundant in ramified cells, where they appeared to traverse from one process to another with no apparent anchoring at MTOCs. The increase in acetylated and detyrosinated microtubules was paralleled by an increased stability against nocodazole-induced microtubule disassembly and by a lower rate of change in the length of the processes. Staining of retinal wholemounts confirmed the presence of acetylated microtubules in ramified microglia in situ. We conclude that during the transition of microglia to a ramified phenotype regulated processes exist, which cause a reorganization of microtubules and a change in composition of the microtubule skeleton resulting in a less dynamic and more stable microtubule network. Intracellular factors that are specifically involved in microtubule stabilization in ramified microglia need to be identified in future research and may provide a useful criterion for defining ramified microglia.
在原位和体外，小胶质细胞可呈现不同形态，一般认为这些形态反映了不同的生理活动。两种极端形式是阿米巴样小胶质细胞和分枝状小胶质细胞。为了研究分化过程中的细胞骨架变化，我们使用特定的细胞培养系统从小鼠脑部分离出阿米巴样或分枝状小胶质细胞培养物。在增殖、分泌、受体表达和吞噬作用方面，分枝状小胶质细胞通常活性较低。我们发现，向分枝状表型的转变伴随着乙酰化和去酪氨酸化微管蛋白相对含量的增加。在阿米巴样细胞中，修饰的微管局限于靠近微管组织中心（MTOC）的区域，而在分枝状细胞中，乙酰化微管丰富，它们似乎从一个突起穿过到另一个突起，在MTOC处没有明显的锚定。乙酰化和去酪氨酸化微管的增加伴随着对诺考达唑诱导的微管解聚稳定性的增加以及突起长度变化率的降低。视网膜整装染色证实原位分枝状小胶质细胞中存在乙酰化微管。我们得出结论，在小胶质细胞向分枝状表型转变过程中，存在调节过程，导致微管重组和微管骨架组成变化，从而形成动态性较低且更稳定的微管网络。未来研究需要确定分枝状小胶质细胞中具体参与微管稳定的细胞内因子，这可能为定义分枝状小胶质细胞提供有用标准。
