Horvath Ryan J, Nutile-McMenemy Nancy, Alkaitis Matthew S, Deleo Joyce A
Department of Pharmacology, Dartmouth Medical School, Hanover, New Hampshire, USA.
J Neurochem. 2008 Oct;107(2):557-69. doi: 10.1111/j.1471-4159.2008.05633.x. Epub 2008 Sep 18.
Microglial cells are hematopoietically derived monocytes of the CNS and serve important neuromodulatory, neurotrophic, and neuroimmune roles. Following insult to the CNS, microglia develop a reactive phenotype, migrate to the site of injury, proliferate, and release a range of proinflammatory, anti-inflammatory, and neurotrophic factors. Isolation of primary microglial cell cultures has been an integral step in elucidating the many roles of these cells. In addition to primary microglial cells, several immortalized cell lines have been created to model primary microglia in vitro, including murine-derived BV-2 cells and rat derived highly aggressive proliferating immortalized (HAPI) cells. Here, we compare rat primary microglial, BV-2, and HAPI cells in experiments assessing migration, expression of activation markers, and production and release of nitric oxide, cytokines, and chemokines. BV-2 and HAPI cells responded similarly to primary microglia in experiments assessing migration, ionized calcium binding adaptor molecule 1 expression, and nitric oxide release. However, BV-2 and HAPI cells did not model primary microglia in experiments assessing tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, and monocyte chemoattractant protein-1 expression and release and phospho-extracellular signal-regulated kinase 44/42 expression following lipopolysaccharide treatment. These results indicate that BV-2 and HAPI cell cultures only partially model primary microglia and that their use should therefore be carefully considered.
小胶质细胞是源自造血系统的中枢神经系统单核细胞,发挥着重要的神经调节、神经营养和神经免疫作用。中枢神经系统受损后,小胶质细胞会呈现出反应性表型,迁移至损伤部位,增殖并释放一系列促炎、抗炎和神经营养因子。分离原代小胶质细胞培养物是阐明这些细胞多种作用的重要步骤。除了原代小胶质细胞外,还创建了几种永生化细胞系以在体外模拟原代小胶质细胞,包括源自小鼠的BV-2细胞和源自大鼠的高侵袭性增殖永生化(HAPI)细胞。在此,我们在评估迁移、激活标志物表达以及一氧化氮、细胞因子和趋化因子的产生与释放的实验中,对大鼠原代小胶质细胞、BV-2细胞和HAPI细胞进行了比较。在评估迁移、离子化钙结合衔接分子1表达和一氧化氮释放的实验中,BV-2细胞和HAPI细胞对原代小胶质细胞的反应相似。然而,在评估脂多糖处理后肿瘤坏死因子-α、白细胞介素-1β、白细胞介素-6和单核细胞趋化蛋白-1的表达与释放以及磷酸化细胞外信号调节激酶44/42表达的实验中,BV-2细胞和HAPI细胞无法模拟原代小胶质细胞。这些结果表明,BV-2细胞和HAPI细胞培养物仅部分模拟原代小胶质细胞,因此在使用时应谨慎考虑。