Phospholipids modulate superoxide and nitric oxide production by lipopolysaccharide and phorbol 12-myristate-13-acetate-activated microglia
Phospholipids modulate superoxide and nitric oxide production by lipopolysaccharide and phorbol 12-myristate-13-acetate-activated microglia
复制标题
DOI：
10.1016/j.neuint.2006.10.006
复制
发表时间：
2007-02-01
影响因子：
4.2
通讯作者：
Kanba, Shigenobu
中科院分区：
文献类型：
--
作者：
Hashioka, Sadayuki;Han, Youn-Hee;Kanba, Shigenobu
小胶质细胞活化和炎症过程与许多神经退行性疾病的发病机制有关。近年来，小胶质细胞活化后产生的超氧阴离子（O-center dot（2）-）与一氧化氮（NO）的反应产物过氧亚硝酸根（ONOO-）被证实是小胶质细胞活化后神经毒性的主要介质。另一方面，磷脂如磷脂酰丝氨酸（PS）和磷脂酰胆碱（PC）已被报道可调节吞噬细胞的免疫功能。因此，我们使用电子自旋共振（ESR）自旋捕获技术，分别采用DEPMPO和Griess反应，评价了包含PS和PC（PS/PC脂质体）或仅包含PC（PC脂质体）的脂质体对脂多糖（LPS）/佛波醇12-肉豆蔻酸酯-13-乙酸酯（PMA）激活的小胶质细胞产生中心点O-2（-）和NO的影响。用PS/PC脂质体或PC脂质体预处理可明显抑制LPS/PMA激活的小胶质细胞的O-中心点（2）-加合物信号强度，并呈剂量依赖性。此外，PS/PC脂质体预处理也显着减少LPS/PMA诱导的小胶质细胞NO的产生。与此相反，PC脂质体预处理对NO的产生没有影响。这些结果表明，PS/PC脂质体可以抑制小胶质细胞的NO和中心点O-2（-）的产生，从而可能阻止随后的ONOO-的形成。因此，PS/PC脂质体似乎通过抑制微脂激活而具有神经保护和抗氧化性质。(c)2006爱思唯尔有限公司保留所有权利。
Microglial activation and inflammatory processes have been implicated in the pathogenesis of a number of neurodegenerative disorders. Recently, peroxynitrite (ONOO-), the reaction product of superoxide (O-center dot(2)-) and nitric oxide (NO) both of which can be generated by activated microglia, has been demonstrated to act as a major mediator in the neurotoxicity induced by activated microglia. On the other hand, phospholipids such as phosphatidylserine (PS) and phosphatidy1choline (PC) have been reported to modulate the immune function of phagocytes. We therefore evaluated the effects of liposomes which comprise both PS and PC (PS/PC liposomes) or PC only (PC liposomes) regarding the production of both center dot O-2(-) and NO by lipopolysaccharide (LPS)/phorbol 12-myristate- 13-acetate (PMA)-activated microglia using electron spin resonance (ESR) spin trap technique with a DEPMPO and Griess reaction, respectively. Pretreatment with PS/PC liposomes or PC liposomes considerably inhibited the signal intensity of O-center dot(2)- adduct associated with LPS/PMA-activated rnicroglia in a dose-dependent manner. In addition, pretreatment with PS/PC liposomes also significantly reduced LPS/PMA-induced microglial NO production. In contrast, pretreatment with PC liposomes had no effect on the NO production. These results indicate that PS/PC liposomes can inhibit the microglial production of both NO and center dot O-2(-), and thus presumably prevent a subsequent formation of ONOO-. Therefore, PS/PC liposomes appear to have both neuroprotective and anti-oxidative properties through the inhibition of micro-lial activation. (c) 2006 Elsevier Ltd. All rights reserved.