The polarization of Th1/Th2 balance is dependent on the intracellular thiol redox status of macrophages due to the distinctive cytokine production
The polarization of Th1/Th2 balance is dependent on the intracellular thiol redox status of macrophages due to the distinctive cytokine production
复制标题
DOI：
10.1093/intimm/14.2.201
复制
发表时间：
2002-02-01
影响因子：
4.4
通讯作者：
Hamuro, J
中科院分区：
文献类型：
--
作者：
Murata, Y;Shimamura, T;Hamuro, J
我们一直在提出两类巨噬细胞（Mp）的功能区分，即还原性巨噬细胞（RMp）与谷胱甘肽的细胞内含量高和氧化性巨噬细胞（OMp）与减少的内容。在本文中，我们将提供证据表明，T（h）1/T（h）2平衡是由RMp和OMp之间的平衡调节，由于IL-12与IL-6和IL-10的不同生产。在体内应用N-乙酰-L-半胱氨酸或谷胱甘肽单乙酯诱导RMp，L-胱氨酸衍生物、马来酸二乙酯或L-丁硫氨酸-[S，R]-亚砜亚胺诱导OMp。任意称为OMp的Mp显示IL-6和IL-10产生增加，而NO和IL-12产生减少。RMp引起相互反应，即升高IL-12和NO产生，并降低IL-6和IL-10产生。OMp或RMp的细胞因子倾向相互转换。还通过使用auto-MACS纯化的F4/80（+）Mp（无粘附）确认了结果。有趣的是，IFN-γ诱导RMp并增加NO的产生，同时减少IL-6的产生，而IL-4诱导OMp并增加IL-6的产生。CD 4（+）CD 44（-）幼稚T（h）0细胞在IL-2存在下，根据培养最初24 h期间RMp或OMp的存在，从卵清蛋白特异性TCR转基因小鼠脾细胞优先分化为T（h）1或T（h）2细胞。总之，RMp感应可以产生RMp/T（h）1电路的放大环路，而OMp感应可以产生OMp/T（h）2电路的放大环路。研究结果表明，由于细胞内谷胱甘肽的改变，Mp功能的改变可能在炎症的病理进展中起相关作用。
We have been proposing the functional discrimination of two classes of macrophages (Mp), i.e. reductive macrophages (RMp) with a high intracellular content of glutathione and oxidative macrophages (OMp) with a reduced content. In this paper we will present the evidence that the T(h)1/T(h)2 balance is regulated by the balance between RMp and OMp due to the disparate production of IL-12 versus IL-6 and IL-10. RMp were induced by in vivo application of N-acetyl-L-cysteine or glutathione monoethylester and OMp by L-cystine derivatives, diethyl maleate or L-buthionine-[S,R]-sulfoximine. The Mp arbitrarily called OMp showed elevated IL-6 and IL-10 production, and reduced NO and IL-12 production. The RMp elicited a reciprocal response, i.e. elevated IL-12 and NO production, and reduced IL-6 and IL-10 production. The cytokine propensities of OMp or RMp were inter-converted to each other. The results were also confirmed by using auto-MACS purified F4/80(+) Mp without adherence. Interestingly, IFN-gamma induced RMp and augmented NO generation with decreased production of IL-6, whilst IL-4 induced OMp and augmented IL-6 production. CD4(+)CD44(-) naive T(h)0 cells were differentiated preferentially either to T(h)1 or T(h)2 cells, depending on the presence of RMp or OMp during the initial 24 h of culture, from ovalbumin-specific TCR-transgenic mouse spleen cells in the presence of IL-2. Taken together, RMp induction may generate the amplification loop of a RMp/T(h)1 circuit and OMp that of OMp/T(h)2. The findings implicate that the alteration In Mp functions because altered intracellular glutathione may play a relevant role in the pathological progression of Inflammation.