Negative feedback regulation of activated macrophages via Fas-mediated apoptosis.
Negative feedback regulation of activated macrophages via Fas-mediated apoptosis.
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通过 Fas 介导的细胞凋亡对活化巨噬细胞进行负反馈调节。
DOI：
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发表时间：
2000
期刊：
影响因子：
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通讯作者：
T. Ogihara
中科院分区：
文献类型：
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作者：
T. Niinobu;K. Fukuo;O. Yasuda;M. Tsubakimoto;M. Mogi;H. Nishimaki;S. Morimoto;T. Ogihara
细胞凋亡是清除活化巨噬细胞的关键事件。在这里，我们表明，Fas介导的细胞凋亡可能参与了负反馈调节活化的巨噬细胞的机制。细胞因子激活的巨噬细胞释放高水平的一氧化氮（NO），诱导巨噬细胞本身的凋亡。这种NO诱导的巨噬细胞凋亡被与Fas配体（FasL）结合并阻止其与内源性细胞表面Fas相互作用的Fas-Fc嵌合分子抑制。高水平的NO刺激可溶性形式的FasL的释放，其被基质金属蛋白酶抑制剂KB-8301抑制。高浓度的NO也可上调巨噬细胞Fas mRNA的表达。此外，从Fas缺乏小鼠分离的巨噬细胞对NO诱导的凋亡具有抗性。最后，通过半胱天冬酶抑制剂抑制细胞凋亡增加了活化的巨噬细胞的过氧化物产生。这些结果表明，从活化的巨噬细胞释放的高水平的NO可能促进Fas介导的巨噬细胞凋亡，这可能是消除和下调血管壁中活化的巨噬细胞的负反馈机制。
Apoptosis is a critical event for eliminating activated macrophages. Here we show that Fas-mediated apoptosis may participate in the mechanism of negative feedback regulation of activated macrophages. Cytokine-activated macrophages released high levels of nitric oxide (NO) that induced apoptosis in macrophages themselves. This NO-induced macrophage apoptosis was inhibited by a Fas-Fc chimeric molecule that binds to Fas ligand (FasL) and prevents its interaction with endogenous cell surface Fas. High levels of NO stimulated the release of the soluble form of FasL that was inhibited by a matrix metalloproteinase inhibitor KB-8301. High levels of NO also upregulated the expression of Fas mRNA in macrophages. In addition, macrophages isolated from Fas-lacking mice were resistant to NO-induced apoptosis. Finally, inhibition of apoptosis by a caspase inhibitor augmented peroxide production from activated macrophages. These findings suggest that high levels of NO released from activated macrophages may promote the Fas-mediated macrophage apoptosis that may be a negative feedback mechanism for elimination and the downregulation of activated macrophages in the vessel wall.
影响因子：
37.8
作者：
P. Shah;E. Falk;J. Badimón;A. Fernández-Ortiz;A. Mailhac;G. Villareal-Levy;J. Fallon;J. Regnstrom;V. Fuster
通讯作者：
P. Shah;E. Falk;J. Badimón;A. Fernández-Ortiz;A. Mailhac;G. Villareal-Levy;J. Fallon;J. Regnstrom;V. Fuster
影响因子：
4.4
作者：
D. Mangan;S. Wahl
通讯作者：
D. Mangan;S. Wahl
影响因子：
15.9
作者：
Gosling, J;Slaymaker, S;Charo, IF
通讯作者：
Charo, IF