Impairment of human neutrophil oxidative burst by polychlorinated biphenyls: inhibition of superoxide dismutase activity
Impairment of human neutrophil oxidative burst by polychlorinated biphenyls: inhibition of superoxide dismutase activity
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DOI：
10.1002/jlb.63.2.216
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发表时间：
1998-02-01
影响因子：
5.5
通讯作者：
Robinson, JP
中科院分区：
文献类型：
--
作者：
Narayanan, PK;Carter, WO;Robinson, JP
我们报告了一种新的机制的证据，通过这种机制，多氯联苯可能作为一种有效的炎症诱导剂，Aroclor 1242（A1242），一种多氯联苯混合物，和2，2 '，4，4'-四氯联苯（PCB 47），A1242的一种成分，产生相同的作用模式，通过抑制抗氧化酶超氧化物歧化酶，将O-2（-）转化为H2 O2。在用佛波醇12-肉豆蔻酸酯13-乙酸酯刺激之前，将中性粒细胞与A1242或PCB 47预孵育，增强了呼吸爆发，与未暴露的激动剂刺激的中性粒细胞相比，细胞内O-2（-）产生沿着显著增加，H2 O2产生显著减少。这在生理学相关的情况下也是明显的，其中用A1242预孵育的中性粒细胞随后用N-甲酰基-L-甲硫氨酰基-L-亮氨酰基-L-苯丙氨酸和肿瘤坏死因子-α的组合刺激。牛铜锌超氧化物歧化酶（EC 1.15.1.1）与A1242或PCB 47在无细胞系统中孵育逆转了酶介导的6-羟基多巴胺自氧化抑制，表明多氯联苯抑制超氧化物歧化酶活性。中性粒细胞中超氧化物歧化酶活性低导致自由基产生与抗氧化防御机制之间的不平衡，从而导致组织损伤并加速中性粒细胞凋亡的发生。
We report evidence of a novel mechanism by which polychlorinated biphenyls might act as potent inducers of inflammation, Aroclor 1242 (A1242), a polychlorinated biphenyl mixture, and 2,2',4,4'-tetrachlorobiphenyl (PCB47), a constituent of A1242 that produces the same patterns of effects, impaired the oxidative burst of human neutrophils by inhibiting the antioxidant enzyme superoxide dismutase, which converts O-2(-) to H2O2. Pre-incubation of neutrophils with A1242 or PCB47 before stimulation with phorbol 12-myristate 13-acetate heightened the respiratory burst, producing a significant increase in intracellular O-2(-) production along with a significant decrease in H2O2 production compared with unexposed agonist-stimulated neutrophils. This was also evident in a physiologically relevant situation in which neutrophils pre-incubated with A1242 were subsequently stimulated with a combination of N-formyl-L-methionyl-L-leucyl-L-phenylalanine and tumor necrosis factor-alpha. Incubation of bovine copper-zinc superoxide dismutase (EC 1.15.1.1) with A1242 or PCB47 in a cell-free system reversed the enzyme-mediated inhibition of 6-hydroxydopamine autoxidation, indicating that polychlorinated biphenyl inhibited superoxide dismutase activity. Low superoxide dismutase activity in neutrophils leads to imbalances between production of free radicals and antioxidant defense mechanisms, which can in turn induce tissue damage and hasten the onset of neutrophil apoptosis.