Metal-induced modulation of nitric oxide production in vitro by murine macrophages: lead, nickel, and cobalt utilize different mechanisms.
Metal-induced modulation of nitric oxide production in vitro by murine macrophages: lead, nickel, and cobalt utilize different mechanisms.
复制标题
金属诱导的小鼠巨噬细胞体外一氧化氮产生调节：铅、镍和钴利用不同的机制。
DOI：
10.1006/taap.1996.0320
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发表时间：
1996
影响因子：
3.8
通讯作者：
Lawrence,DA
中科院分区：
文献类型：
--
作者：
Tian,L;Lawrence,DA
巨噬细胞（Mφ）可诱导产生一氧化氮（NO），一氧化氮对巨噬细胞行使各种功能至关重要。我们以前报道过一种环境毒物铅（Pb）可以显著抑制小鼠脾Mφs产生NO。本文对金（Au）、镉（Cd）、钴（Co）、铬（Cr）、铜（Cu）、汞（Hg）、镍（Ni）和锌（Zn）这八种额外的金属离子进行了评估。除Pb外，Hg和Cd显著抑制细胞因子（干扰素-γ和肿瘤坏死因子-α）刺激小鼠m - φs产生NO。Au和Cu也有抑制作用，但低于Pb、Hg和Cd。相反，Cr和Zn没有调节作用，Ni和Co显著促进细胞因子刺激的m - φs产生NO。Ni和Co的增强作用被精氨酸类似物-单甲基精氨酸所抑制。当添加到已表达诱导型NO合成酶（iNOS）的无细胞（活化的Mφ裂解液）NO生成系统中时，金属表现出不同的激活/抑制特征。Cr、Cu、Pb和Zn适度抑制iNOS，这表明它们可能直接改变酶或辅助因子的活性。Cd、Hg、Mg、Ni或Co对无细胞系统产生NO没有显著影响。暴露于pb的Mφs对NO产生的抑制不是由于iNOS表达的减少，也不限于其对iNOS的适度直接抑制；因此，其他机制必须对pb诱导的Mφ对NO产生的有效抑制负责。镍或钴均可诱导iNOS蛋白的大量增加。总的来说，这些观察结果提供了额外的见解，通过抑制或增强NO产生的金属可能是致病的，分别通过抑制防御机制或诱导超敏反应。
Macrophages (Mφ) can be induced to produce nitric oxide (NO), which has been suggested to be important for macrophages to exercise various functions. We have previously reported that an environmental toxicant, lead (Pb), can significantly inhibit NO production by murine splenic Mφs. Herein, eight additional metal ions, gold (Au), cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), mercury (Hg), nickel (Ni), and zinc (Zn), were assessed. In addition to Pb, Hg and Cd significantly suppressed NO production by cytokine (interferon-γ and tumor necrosis factor-α)-stimulated murine Mφs. Au and Cu also were inhibitory, but less than Pb, Hg, and Cd. In contrast, Cr and Zn were not modulatory, and Ni and Co significantly enhanced NO production by cytokine-stimulated Mφs. The enhancement by Ni and Co was inhibited by the arginine analogN-monomethylarginine. The metals showed different activating/inhibiting profiles when added to a cell-free (activated Mφ lysate) NO-producing-system in which inducible NO synthase (iNOS) is already expressed. Cr, Cu, Pb, and Zn moderately suppressed iNOS, which suggests that they may directly modify enzyme or cofactor activity. Cd, Hg, Mg, Ni, or Co did not produce any significant effect on NO production by the cell-free system. Inhibition of NO production by Pb-exposed Mφs was not due to decreased expression of iNOS nor limited to its modest direct inhibition of iNOS; thus, other mechanism(s) must be accountable for the efficient Pb-induced inhibition of NO production by Mφ. Ni or Co did induce a substantial increase of iNOS protein. Overall, these observations provide additional insight into the means by which metals via inhibition or enhancement of NO production may be pathogenic, by suppression of defense mechanisms or induction of hypersensitivity, respectively.