Becher B, D'Souza S D, Troutt A B, Antel J P
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Quebec, Canada.
Neuroscience. 1998 May;84(2):627-34. doi: 10.1016/s0306-4522(97)00455-7.
Fas (APO-1/CD95) is a cell surface receptor, initially identified in lymphoid cells, but more recently detected in the central nervous system under pathologic conditions. Ligation of the fas receptor by fas ligand or by agonist antibodies induces apoptotic cell death in most fas-expressing cells. In the current study, using dissociated cultures of human fetal central nervous system-derived cells, we detected fas expression on astrocytes but not on neurons. Such expression differs from our previous results using cultures of human adult central nervous system-derived cells, which demonstrated fas expression on oligodendrocytes but not on astrocytes; the oligodendrocytes were susceptible to cell death via this pathway. Using multiple assays of cell death, including nuclear propidium iodide and TUNEL staining to detect nuclear-directed injury, cytofluorometric propidium iodide inclusion, and lactate dehydrogenase release to detect membrane-directed injury, we found that fas ligation, however, did not induce cell death in the cultured fetal astrocytes. Cytokines that augmented (gamma-interferon) or inhibited (interleukin-4) fetal astrocyte proliferation did not alter fas expression or resistance to fas ligation. Cells obtained immediately ex vivo from human fetal but not from adult central nervous system tissue expressed fas; such expression was restricted to astrocytes as assessed by dual-stain immunohistochemistry. The fetal central nervous system cells did not express fas ligand. Our findings indicate that fas expression on central nervous system cells may reflect their state of maturity; expression may not, however, always be coupled to susceptibility to cell death via this pathway.
Fas（APO-1/CD95）是一种细胞表面受体，最初在淋巴细胞中被鉴定出来，但最近在病理条件下的中枢神经系统中也被检测到。Fas受体与Fas配体或激动剂抗体结合，可诱导大多数表达Fas的细胞发生凋亡性细胞死亡。在本研究中，我们使用人胎儿中枢神经系统来源细胞的解离培养物，检测到星形胶质细胞上有Fas表达，而神经元上没有。这种表达与我们之前使用人成人中枢神经系统来源细胞培养物的结果不同，之前的结果显示少突胶质细胞上有Fas表达，而星形胶质细胞上没有；少突胶质细胞通过该途径易发生细胞死亡。我们使用多种细胞死亡检测方法，包括用碘化丙啶和TUNEL染色检测细胞核定向损伤、用细胞荧光术检测碘化丙啶摄取以及用乳酸脱氢酶释放检测细胞膜定向损伤，发现Fas连接并未诱导培养的胎儿星形胶质细胞死亡。增强（γ干扰素）或抑制（白细胞介素-4）胎儿星形胶质细胞增殖的细胞因子并未改变Fas表达或对Fas连接的抗性。从人胎儿而非成人中枢神经系统组织立即离体获取的细胞表达Fas；通过双重染色免疫组织化学评估，这种表达仅限于星形胶质细胞。胎儿中枢神经系统细胞不表达Fas配体。我们的研究结果表明，中枢神经系统细胞上的Fas表达可能反映其成熟状态；然而，这种表达可能并不总是与通过该途径发生细胞死亡的易感性相关联。
