Activation of NF kappa B by the respiratory burst of macrophages
Activation of NF kappa B by the respiratory burst of macrophages
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DOI：
10.1016/0891-5849(96)00178-5
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发表时间：
1996-01-01
影响因子：
7.4
通讯作者：
Forman, HJ
中科院分区：
文献类型：
--
作者：
Kaul, N;Forman, HJ
过氧化氢和其他还原氧物种被认为是转录因子NF kappa B的激活剂。受刺激的巨噬细胞产生超氧化物和过氧化氢(呼吸爆发)。我们验证了这些物种的产生可能是大鼠肺泡巨噬细胞和J774A.1小鼠单核/巨噬细胞系中核因子kappa B激活途径的一部分的假设。佛波醇肉豆蔻酸酯(PMA)和ADP刺激呼吸爆发，在这两个细胞中都能引起核因子kappaB的激活。过氧化氢酶可抑制核因子kappaB的激活，而超氧化物歧化酶对核因子kappaB的抑制作用很小。因此，H_2O_2是呼吸爆发相关的核因子-kappaB活化的主要因素。通过过氧化氢酶取消核因子kappaB的激活也表明，中间信号通路，如蛋白激酶C激活或细胞内游离钙升高，不可能参与其中。外源性双氧水以大于或等于50mU M(大于或等于50nmol/10(6)巨噬细胞)的形式加入，也可激活巨噬细胞中的核因子-kappaB。然而，刺激的肺泡巨噬细胞在30分钟内产生的最大内源性H_2O_2，对于PMA刺激小于或等于1.3nmol H_2O_2/10(6)细胞，对于ADP刺激小于或等于0.2nmol H_2O_2/10(6)细胞。因此，与外源过氧化氢的需求量相比，内源性过氧化氢产生产生核因子kappa B所需的相对较少的量。随着过氧化氢的迅速扩散和消耗，这些结果表明，内源产生的过氧化氢的作用部位可能接近其起源--质膜。
H2O2 and other reduced oxygen species have been proposed as activators of the transcription factor, NF kappa B. Stimulated macrophages produce superoxide and H2O2 (the respiratory burst). We tested the hypothesis that production of these species could serve as part of the NF kappa B activation pathway in rat alveolar macrophages and the J774A.1 mouse monocyte/macrophage cell line. Phorbol myristate acetate (PMA) and ADP, which stimulate the respiratory burst, caused NF kappa B activation in both cells. Catalase abolished NF kappa B activation, while superoxide dismutase produced little inhibition. Thus, H2O2 was the principal agent of respiratory burst-associated NF kappa B activation. Abolition of NF kappa B activation by catalase also suggested that intermediate signaling pathways, such as protein kinase C activation or intracellular free calcium elevation must not be involved. Exogenous H2O2 added as a bolus greater than or equal to 50 mu M (greater than or equal to 50 nmol/10(6) macrophages) also activated NF kappa B in macrophages. Nevertheless, the maximum endogenous production of H2O2 by stimulated alveolar macrophages during a 30-min incubation was less than or equal to 1.3 nmol H2O2/10(6) cells for PMA stimulation and less than or equal to 0.2 nmol H2O2/10(6) cells for ADP stimulation. Thus, relatively little endogenous H2O2 generation was required to produce NF kappa B activation compared to the required amount of exogenous H2O2. As H2O2 rapidly diffuses and is consumed, these results suggest that the site of action for endogenously generated H2O2 is probably close to its origin, the plasma membrane.