Pure albumin is a potent trigger of calcium signalling and proliferation in microglia but not macrophages or astrocytes
Pure albumin is a potent trigger of calcium signalling and proliferation in microglia but not macrophages or astrocytes
复制标题
DOI：
10.1111/j.1471-4159.2005.02982.x
复制
发表时间：
2005-03-01
影响因子：
4.7
通讯作者：
Pocock, JM
中科院分区：
文献类型：
--
作者：
Hooper, C;Taylor, DL;Pocock, JM
小胶质细胞活化与神经退行性疾病的神经毒性有关。脑内白蛋白水平升高与阿尔茨海默病、多发性硬化症和中风的病理有关，其中血脑屏障损伤明显。我们在这里报道，用纯白蛋白或含有脂肪酸和免疫球蛋白的白蛋白（部分V）处理原代培养的小胶质细胞和N9小胶质细胞系，诱导细胞内钙升高。细胞内钙的增加是通过Src酪氨酸激酶和磷脂酶c介导的。白蛋白诱导的钙反应与小胶质细胞增殖相结合，BAPTA、U73122和PP2可以阻止这种反应，但thapsigargin无法模仿。相比之下，腹膜巨噬细胞对白蛋白或部分V诱导的钙反应和增殖有抗性，而原代培养的星形胶质细胞或TSA-3星形胶质细胞对部分V白蛋白有反应，但对纯白蛋白没有反应。此外，小脑颗粒神经元对白蛋白没有反应。这些数据表明，在涉及血脑屏障损伤的病理情况下，白蛋白可能在小胶质细胞激活中发挥作用，并且小胶质细胞对白蛋白的特异性反应允许区分小胶质细胞、血源性巨噬细胞、星形胶质细胞和神经元的信号反应。
Microglial activation is implicated in the neurotoxicity of neurodegenerative diseases. Raised intracerebral levels of albumin are associated with the pathology of Alzheimer's disease, multiple sclerosis, and stroke where blood-brain barrier damage is evident. We report here that treatment of primary cultured microglia and the N9 microglial cell line with pure albumin, or albumin in which fatty acids and immunoglobulins remain attached (fraction V), induced a rise in intracellular calcium. This rise in intracellular calcium was mediated via Src tyrosine kinase and phospholipase C. The albumin-induced calcium response was coupled to microglial proliferation, which was prevented by BAPTA, U73122 or PP2 but not mimicked by thapsigargin. In contrast, peritoneal macrophages were resistant to albumin- or fraction V-induced calcium responses and proliferation, whilst primary cultured astrocytes or the TSA-3 astrocyte cell line were responsive to fraction V albumin but not pure albumin. Furthermore, cerebellar granule neurones did not respond to albumin. These data suggest that albumin may play a role in microglial activation in pathological situations involving blood-brain barrier impairment, and that the specific responses of microglia to albumin allow a distinction to be made between the signalling responses of microglia, blood-borne macrophages, astrocytes and neurones.