ATP-mediated cytotoxicity in microglial cells
ATP-mediated cytotoxicity in microglial cells
复制标题
DOI：
10.1016/s0028-3908(97)00137-8
复制
发表时间：
1997-09-01
影响因子：
4.7
通讯作者：
DiVirgilio, F
中科院分区：
文献类型：
--
作者：
Ferrari, D;Chiozzi, P;DiVirgilio, F
已知小胶质细胞表达P2 Y和P2 X亚型的细胞外ATP的嘌呤能受体。功能研究表明，原代小鼠小胶质细胞和N9和N13小胶质细胞系均表达成孔P2 Z/P2 X（7）受体。在这里，我们用特异性多克隆抗体鉴定了N9和N13细胞中该受体的存在，并表明表达P2 Z/P2 X（7）受体的小胶质细胞对ATP介导的细胞毒性非常敏感，而选择缺乏该受体的克隆则具有抗性。用P2 X（7）（而不是P2 X（2））受体cDNA转染HEK 293细胞可使其对ATP介导的细胞毒性敏感。形态学和生化分析表明，ATP依赖性的细胞死亡的小胶质细胞发生凋亡。最后，小胶质细胞释放ATP通过非溶解机制时，细菌内毒素激活，从而表明嘌呤能自分泌/旁分泌回路的操作。(C)1997年爱思唯尔科学有限公司
Microglial cells are known to express purinergic receptors for extracellular ATP of both the P2Y and P2X subtypes. Functional studies have shown that both primary mouse microglial cells and the N9 and N13 microglial cell lines express the pore-forming P2Z/P2X(7) receptor. Here we identify the presence of this receptor in N9 and N13 cells with a specific polyclonal Ab and show that microglial cells expressing the P2Z/P2X(7) receptor are exquisitively sensitive to ATP-mediated cytotoxicity while clones selected for the lack of this receptor are resistant. Transfection of HEK293 cells with P2X(7) (but not P2X(2)) receptor cDNA confers susceptibility to ATP-mediated cytotoxicity. Morphological and biochemical analysis suggests that ATP-dependent cell death in microglial cells occurs by apoptosis. Finally, microglial cells release ATP via a nonlytic mechanism when activated by bacterial endotoxin, thus suggesting the operation of a purinergic autocrine/paracrine loop. (C) 1997 Elsevier Science Ltd.