Guillemin G, Boussin F D, Le Grand R, Croitoru J, Coffigny H, Dormont D
Service de Neurovirologie, CEA, DSV/DRM/SSA/IPSC, Fontenay-aux-Roses, France.
Glia. 1996 Jan;16(1):71-80. doi: 10.1002/(SICI)1098-1136(199601)16:1<71::AID-GLIA8>3.0.CO;2-E.
In the brain, granulocyte-macrophage colony stimulating factor (GM-CSF) may be released by infiltrated cells of the immune system including T and B lymphocytes and mononuclear phagocytes, but also by nervous system resident cells such as microglia and astrocytes. Astrocyte-secreted GM-CSF may play an important role in enhancing the local inflammatory response to central nervous system (CNS) injury and in recruting microglia and activated macrophages. In this study, we demonstrated that GM-CSF, as TNF alpha and IL 6, stimulates in vitro proliferation of simian astrocytes in primary cultures. Results were confirmed by blocking experiments performed with a specific neutralizing mAb directed against GM-CSF. Furthermore, we demonstrated that GM-CSF mediates its effect on these cells through the alpha subunit of the GM-CSF receptor which is constitutively expressed at the membrane of the cultured simian astrocytes as assessed by immunofluorescence. GM-CSF effects on astrocytes could be involved in astrocytosis, a hallmark of various neurological injuries and in inflammatory processes in an autocrine manner.
在大脑中,粒细胞巨噬细胞集落刺激因子(GM-CSF)可能由包括T和B淋巴细胞以及单核吞噬细胞在内的免疫系统浸润细胞释放,也可由小胶质细胞和星形胶质细胞等神经系统驻留细胞释放。星形胶质细胞分泌的GM-CSF可能在增强对中枢神经系统(CNS)损伤的局部炎症反应以及募集小胶质细胞和活化巨噬细胞方面发挥重要作用。在本研究中,我们证明GM-CSF与肿瘤坏死因子α(TNFα)和白细胞介素6(IL 6)一样,能刺激原代培养的猿猴星形胶质细胞在体外增殖。用针对GM-CSF的特异性中和单克隆抗体进行的阻断实验证实了该结果。此外,我们证明GM-CSF通过GM-CSF受体的α亚基介导其对这些细胞的作用,通过免疫荧光评估发现该亚基在培养的猿猴星形胶质细胞膜上组成性表达。GM-CSF对星形胶质细胞的作用可能以自分泌方式参与星形细胞增生,这是各种神经损伤的一个标志以及炎症过程。