Kanemaru K, Meckelein B, Marshall D C, Sipe J D, Abraham C R
Department of Medicine, Boston University School of Medicine, MA 02118, USA.
Neurobiol Aging. 1996 Sep-Oct;17(5):767-71. doi: 10.1016/0197-4580(96)00111-x.
Activated astrocytes have been identified as the main source of the serine protease inhibitor alpha 1-antichymotrypsin (ACT), an acute phase protein that is tightly associated with amyloid plaques in Alzheimer's disease (AD) and in normal aged human and monkey brain. We analyzed the synthesis of ACT by cultured murine astrocytes in vitro. The murine astrocytes expressed an ACT-like antigen that crossreacted with antibodies to human ACT. The murine ACT-like protein is secreted by the astrocytes and is able to form an SDS-resistant complex with the serine protease cathepsin G, indicating that the secreted ACT is biologically active. We conclude that cultured primary astrocytes synthesize and secrete murine ACT in an active form. We, therefore, suggest that the ACT present within AD plaques is locally derived from plaque-associated activated astrocytes as a part of a glia-mediated local inflammatory response that is associated with the neurodegeneration seen in AD.
活化的星形胶质细胞已被确定为丝氨酸蛋白酶抑制剂α1 -抗糜蛋白酶（ACT）的主要来源，ACT是一种急性期蛋白，在阿尔茨海默病（AD）以及正常老年人类和猴脑中与淀粉样斑块紧密相关。我们在体外分析了培养的小鼠星形胶质细胞对ACT的合成。小鼠星形胶质细胞表达一种与抗人ACT抗体发生交叉反应的ACT样抗原。小鼠ACT样蛋白由星形胶质细胞分泌，并能够与丝氨酸蛋白酶组织蛋白酶G形成抗SDS复合物，这表明分泌的ACT具有生物活性。我们得出结论，培养的原代星形胶质细胞以活性形式合成并分泌小鼠ACT。因此，我们认为AD斑块中的ACT是局部来源于与斑块相关的活化星形胶质细胞，是神经胶质介导的局部炎症反应的一部分，该反应与AD中所见的神经退行性变有关。
