Microglial cell cytotoxicity of oligodendrocytes is mediated through nitric oxide.
Microglial cell cytotoxicity of oligodendrocytes is mediated through nitric oxide.
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DOI：
10.4049/jimmunol.151.4.2132
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发表时间：
1993-08
影响因子：
4.4
通讯作者：
J. Merrill;L. Ignarro;M. Sherman;J. Melinek;T. Lane
中科院分区：
文献类型：
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作者：
J. Merrill;L. Ignarro;M. Sherman;J. Melinek;T. Lane
大鼠阿米巴样小胶质细胞在体外能溶解大鼠少突胶质细胞。溶解被转化生长因子-β、一氧化氮（NO）产生的拮抗剂以及TNF-α、细胞间粘附分子-1（ICAM-1）和白细胞功能性Ag-1的抗体抑制。阿米巴样小胶质细胞自发产生可检测水平的NO代谢物亚硝酸盐（NO2-）。刺激，如PMA，LPS，和/或IFN-γ诱导微摩尔浓度的NO2-在24小时内。TNF-α增加IFN-γ，但不增加LPS诱导的NO2-产生。与靶少突胶质细胞孵育也以接触依赖性方式增加NO2-产生。NO合成酶拮抗剂、转化生长因子-β和抗TNF-α可抑制NO2-的产生。无论是抗白细胞功能Ag-1，也不抗ICAM-1抑制NO2-生产的小胶质细胞在存在或不存在的少突胶质细胞。事实上，抗ICAM-1治疗增加了NO2-的产生。阿米巴样小胶质细胞杀死少突胶质细胞和NO 2-生产之间存在相关性，这表明NO可能是少突胶质细胞死亡的机制，并可能在多发性硬化症的病变形成中发挥作用。
Rat ameboid microglia are able to lyse rat oligodendrocytes in vitro. The lysis is inhibited by transforming growth factor-beta, antagonists of nitric oxide (NO) production, as well as antibodies to TNF-alpha, intercellular adhesion molecule-1 (ICAM-1), and leukocyte functional Ag-1. Ameboid microglial cells spontaneously produce detectable levels of the NO metabolite nitrite (NO2-). Stimuli such as PMA, LPS, and/or IFN-gamma induce micromolar concentrations of NO2- within 24 h. TNF-alpha increases IFN gamma but not LPS-induced NO2- production. Incubation with target oligodendrocytes also increases NO2- production in a contact-dependent manner. NO2- production is inhibited by NO synthase antagonists, transforming growth factor-beta, and anti TNF-alpha. Neither antileukocyte functional Ag-1 nor anti-ICAM-1 inhibit NO2- production by microglia in the presence or absence of oligodendrocytes. Indeed, anti-ICAM-1 treatment increases NO2- production. There is a correlation between ameboid microglial cell killing of oligodendrocytes and NO2- production suggesting NO may be a mechanism of death of the oligodendrocyte and possibly play a role in lesion formation in multiple sclerosis.