Weinstein D E, Shelanski M L, Liem R K
Department of Pathology, Columbia University College of Physicians and Surgeons, New York, New York 10032.
Glia. 1990;3(2):130-9. doi: 10.1002/glia.440030207.
We have investigated the ability of various cell lines to effect contact-mediated inhibition of astrocytic cells. Of the lines tested, only C17, a mouse cell line from postnatal day 0 cerebellum immortalized by infection with a retroviral construct containing the avian myc gene, and U251, a human astrocytoma line, were able to inhibit the proliferation of astrocytic cells. When co-cultured with either primary astrocytes from rat cerebellum or the U251 line, the C17 cells induced a rapid cessation of glial cell division as well as complex astrocytic process extension. The effects on glial mitosis were cell-dose-dependent, with ten C17 cells/glial cell being the optimal ratio. At this ratio [3H]thymidine incorporation into the U251 cells was reduced by greater than 80% and there was a virtual stasis in glial cell number at 48 hours. Fixed C17 cells as well as partially purified C17 membranes were also potent inhibitors of astrocytic proliferation, suggesting that the gliastatic effect of the C17 cell line is membrane associated. However, neither of these preparations induced astrocytic process formation. We also confirmed earlier reports that U251 cells inhibited their own proliferation in a density-dependent manner but at a lower efficiency than the C17 cells.
我们研究了多种细胞系对星形胶质细胞进行接触介导抑制的能力。在所测试的细胞系中,只有C17(一种来自出生后第0天小脑的小鼠细胞系,通过感染含有禽myc基因的逆转录病毒构建体而永生化)和U251(一种人星形细胞瘤细胞系)能够抑制星形胶质细胞的增殖。当与大鼠小脑的原代星形胶质细胞或U251细胞系共培养时,C17细胞诱导神经胶质细胞分裂迅速停止以及复杂的星形胶质细胞突起延伸。对神经胶质有丝分裂的影响呈细胞剂量依赖性,最佳比例为每1个神经胶质细胞对应10个C17细胞。在此比例下,[3H]胸苷掺入U251细胞的量减少了80%以上,并且在48小时时神经胶质细胞数量几乎停滞。固定的C17细胞以及部分纯化的C17细胞膜也是星形胶质细胞增殖的有效抑制剂,这表明C17细胞系的神经胶质静止作用与膜相关。然而,这些制剂均未诱导星形胶质细胞突起形成。我们还证实了早期的报道,即U251细胞以密度依赖性方式抑制自身增殖,但效率低于C17细胞。