Shinoda M, Hoffer B J, Olson L
Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
J Neural Transplant Plast. 1997 Mar-Jun;6(2):83-96. doi: 10.1155/NP.1997.83.
Glial-cell-line-derived neurotrophic factor (GDNF) stimulates the survival of dopaminergic neurons. Little is known, however, about the possible immune sequelae of GDNF exposure or of exposure to other putative trophic factors. To address these questions, pieces of mesencephalic tissue, substantia nigra, from 15-day-old donor embryos were transplanted into the anterior chamber of the eye of adult male Sprague-Dawley recipient rats. At 5-day intervals, an aliquot (0.5 microgram) of GDNF, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), or cytochrome-C (CC) was injected into the anterior chamber of the eye of the recipients, and the sizes of the transplants were measured. GDNF increased transplant survival and growth. On day 42, all rats were sacrificed, and the grafts were evaluated by cresyl-violet staining and by immunohistochemistry using antibodies raised against neurofilament (NF), tyrosine hydroxylase, or glial fibrillary acidic protein (GFAP), as well as the following monoclonal antibodies: OX-38 anti-CD4, OX-8 anti-CD8, OX-18 anti-MHC class I, OX-6 anti-MHC class II, OX-42 anti-CD11b, R-73 anti-alpha and anti-beta T-cell receptor, and ED1 raised against monocytes/macrophages. BDNF-treated grafts showed only weak immunoreactivity, and even weaker reactions were seen in grafts treated with NT-3, GDNF, or CC. No single immune system marker was significantly elevated in grafts from any treatment group. We used OX-42 and ED1 to study possible alterations of microglial components. Ramified microglial cells were found in GDNF-treated grafts and to a lesser extent in NT-3 and BDNF-treated grafts. ED1-labeled reactive microglial components were found in NT-3- and BDNF-treated grafts. Additionally, large and rounded OX-42-positive phagocytic cells were found in NT-3-treated grafts. Together with our previous finding that GDNF treatment of spinal cord transplants activates immune responses and leads to microglial activation, our data demonstrate that although treatment with GDNF and to some degree with BDNF can enhance immune responses to immunogenic grafts, such as fetal spinal cord grafts, but the trophic factors per se do not elicit any marked response in non-immunogenic grafts like substantia nigra.
胶质细胞源性神经营养因子（GDNF）可刺激多巴胺能神经元的存活。然而，关于暴露于GDNF或其他假定的营养因子可能产生的免疫后遗症，人们了解甚少。为了解决这些问题，将来自15日龄供体胚胎的中脑组织（黑质）移植到成年雄性Sprague-Dawley受体大鼠的眼前房。每隔5天，将一份（0.5微克）GDNF、脑源性神经营养因子（BDNF）、神经营养因子-3（NT-3）或细胞色素C（CC）注入受体大鼠的眼前房，并测量移植组织的大小。GDNF可提高移植组织的存活率和生长速度。在第42天，处死所有大鼠，通过甲酚紫染色以及使用针对神经丝（NF）、酪氨酸羟化酶或胶质纤维酸性蛋白（GFAP）的抗体进行免疫组织化学，以及以下单克隆抗体对移植物进行评估：OX-38抗CD4、OX-8抗CD8、OX-18抗MHC I类、OX-6抗MHC II类、OX-42抗CD11b、R-73抗α和抗β T细胞受体，以及针对单核细胞/巨噬细胞的ED1。BDNF处理的移植物仅显示出微弱的免疫反应性，而在NT-3、GDNF或CC处理的移植物中观察到的反应更弱。任何治疗组的移植物中均未发现单一免疫系统标志物显著升高。我们使用OX-42和ED1研究小胶质细胞成分的可能变化。在GDNF处理的移植物中发现了分支状小胶质细胞，在NT-3和BDNF处理的移植物中也有较少程度的发现。在NT-3和BDNF处理的移植物中发现了ED1标记的反应性小胶质细胞成分。此外，在NT-3处理的移植物中发现了大的圆形OX-42阳性吞噬细胞。连同我们之前的发现，即GDNF处理脊髓移植可激活免疫反应并导致小胶质细胞活化，我们的数据表明，尽管GDNF处理以及在一定程度上BDNF处理可增强对免疫原性移植物（如胎儿脊髓移植物）的免疫反应，但这些营养因子本身不会在像黑质这样的非免疫原性移植物中引发任何明显反应。
