Circulating monocytic cells infiltrate layers of anterograde axonal degeneration where they transform into microglia
Circulating monocytic cells infiltrate layers of anterograde axonal degeneration where they transform into microglia
复制标题
DOI：
10.1096/fj.04-2599fje
复制
发表时间：
2005-01-01
期刊：
影响因子：
4.8
通讯作者：
Priller, J
中科院分区：
文献类型：
--
作者：
Bechmann, I;Goldmann, J;Priller, J
在这项研究中，我们证明了血液来源的单核细胞的浸润和它们的形态转化成小胶质细胞的区域的急性，顺行（沃勒）轴突变性诱导的内嗅皮层病变（ECL）。在接受了绿色荧光蛋白（GFP）转导的骨髓移植物的小鼠中进行ECL，以鉴定脑内的血液来源成分。而在未损伤的半球GFP（+）细胞仅限于血管周围和软脑膜部位，在损伤后24 h（hpl），许多圆形荧光细胞出现在轴突变性的海马区。在72 hpl内，这些GFP（+）细胞获得分枝的小胶质细胞样形态，其在ECL后持续至少7天。从未观察到GFP（+）细胞分化成胶质细胞酸性蛋白（GFAP）（+）星形胶质细胞。为了排除这种募集是辐射或骨髓移植的伪影，在ECL前1天将荧光细胞追踪剂6-羧基荧光素二乙酸酯（CFDA）注射到正常小鼠的脾脏中。在48 hpl和CFDA（+）/ MAC-1（+）时，荧光细胞再次出现在病变部位和沿着轴突变性层，细胞表现出变形样和分枝状形态。因此，血液来源的细胞不仅浸润机械损伤的部位，而且还浸润顺行轴突变性的层，在那里它们容易转化为小胶质细胞样成分。浸润白细胞在促进或调节损伤后可塑性中的作用，例如，通过吞噬抑制生长的髓鞘，现在应该考虑。此外，单核细胞可以作为运输治疗物质，如神经营养因子或半胱天冬酶抑制剂的轴突变性区的车辆。
In this study, we demonstrate the infiltration of blood-derived monocytic cells and their morphologic transformation into microglia in zones of acute, anterograde ( Wallerian) axonal degeneration induced by entorhinal cortex lesion (ECL). ECL was performed in mice which had received green fluorescent protein (GFP)-transduced bone marrow grafts allowing identification of blood-derived elements within the brain. While in the unlesioned hemisphere GFP(+) cells were restricted to perivascular and leptomeningeal sites, many round fluorescent cells appeared in hippocampal zones of axonal degeneration at 24 h post lesion (hpl). Within 72 hpl, these GFP(+) cells acquired ramified, microglia-like morphologies, which persisted for at least 7 days post ECL. Differentiation of GFP(+) cells into glial fibrillary acidic protein (GFAP)(+) astrocytes was never observed. To exclude that this recruitment is an artifact of irradiation or bone marrow transplantation, the fluorescent cell tracker 6-carboxylfluorescein diacetate (CFDA) was injected into spleens of normal mice 1 day before ECL. Again, fluorescent cells appeared at the lesion site and along the layers of axonal degeneration at 48 hpl and CFDA(+)/ MAC-1(+), cells exhibited amoeboid and ramified morphologies. Thus, blood-derived cells infiltrate not only the site of mechanical lesion, but also the layers of anterograde axonal degeneration, where they readily transform into microglia-like elements. A role for infiltrating leukocytes in facilitating or modulating postlesional plasticity, e.g., by phagocytosis of growth-inhibiting myelin should now be considered. Moreover, monocytic cells may serve as vehicles to transport therapeutic substances such as neurotrophic factors or caspase inhibitors to zones of axonal degeneration.