DeWitt D A, Perry G, Cohen M, Doller C, Silver J
Department of Neurosciences, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Exp Neurol. 1998 Feb;149(2):329-40. doi: 10.1006/exnr.1997.6738.
We have developed an in vitro model in which isolated senile plaque (SP) cores are presented to rat microglial cells in culture. Microglia rapidly phagocytosed, broke apart, and cleared SP cores. However, when cocultured with astrocytes, microglial phagocytosis was markedly suppressed, allowing the SPs to persist. Suppression of phagocytosis by astrocytes appears to be a general phenomena since microglia in the presence of astrocytes showed reduced capacity to phagocytose latex beads as well. The astrocyte effect on microglia is related in part to a diffusible factor(s) since astrocyte- but not fibroblast-conditioned media also reduced phagocytosis. These results suggest that while microglia have the capacity to phagocytose and remove SPs, astrocytes which lie in close association to microglia may help prevent the efficient clearance of SP material allowing them to persist in Alzheimer's disease.
我们建立了一种体外模型，在该模型中，将分离出的老年斑（SP）核心呈递给培养中的大鼠小胶质细胞。小胶质细胞迅速吞噬、分解并清除SP核心。然而，当与星形胶质细胞共培养时，小胶质细胞的吞噬作用受到明显抑制，使得SP得以持续存在。星形胶质细胞对吞噬作用的抑制似乎是一种普遍现象，因为在有星形胶质细胞存在的情况下，小胶质细胞吞噬乳胶珠的能力也降低了。星形胶质细胞对小胶质细胞的影响部分与一种可扩散因子有关，因为星形胶质细胞条件培养基（而非成纤维细胞条件培养基）也会降低吞噬作用。这些结果表明，虽然小胶质细胞有能力吞噬和清除SP，但与小胶质细胞紧密相邻的星形胶质细胞可能有助于阻止SP物质的有效清除，从而使其在阿尔茨海默病中持续存在。
