Microbicidal Activity of Vascular Peroxidase 1 in Human Plasma via Generation of Hypochlorous Acid
Microbicidal Activity of Vascular Peroxidase 1 in Human Plasma via Generation of Hypochlorous Acid
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DOI：
10.1128/iai.06337-11
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发表时间：
2012-07-01
影响因子：
3.1
通讯作者：
Cheng, Guangjie
中科院分区：
文献类型：
--
作者：
Li, Hong;Cao, Zehong;Cheng, Guangjie
血红素过氧化物酶家族的成员在宿主防御中发挥重要作用。髓过氧化物酶（MPO）在吞噬细胞中表达，并且是先前报道的能够使用氯离子作为底物在中性pH下形成高度杀微生物的物种次氯酸（HOCl）的唯一动物血红素过氧化物酶。尽管HOCl具有强效的细菌杀灭活性，但不能表达MPO的个体通常在一些真菌感染中仅显示出适度的增加。这可能表明存在冗余的宿主防御机制。血管过氧化物酶1（VPO 1）是血红素过氧化物酶家族中新发现的成员。VPO 1在心血管系统的细胞中表达，并分泌到血流中。在本研究中，我们调查是否VPO 1是能够产生HOCl及其在宿主防御中的作用。与MPO一样，VPO 1在H2 O2和氯化物存在下产生HOC。VPO 1依赖HOC的产生证明了牛磺酸和酪氨酸的氯化，使用质谱。此外，VPO_1/H_2 O_2/Cl ~-体系还能引起一氯双甲酮的氯化反应和5-硫代-2-硝基苯甲酸的氧化反应。血浆中的纯化VPO 1和VPO 1介导依赖于氯化物和H2 O2的细菌杀灭;过氧化物酶抑制剂和H2 O2清除剂过氧化氢酶抑制杀灭。在存在红细胞的情况下，VPO 1对细菌的杀灭作用略有降低。因此，除了MPO之外，VPO 1是血红素过氧化物酶家族的第二个成员，能够在生理条件下产生HOCl。VPO 1可能参与宿主防御，通过生成HOCl介导杀菌活性。
Members of the heme peroxidase family play an important role in host defense. Myeloperoxidase (MPO) is expressed in phagocytes and is the only animal heme peroxidase previously reported to be capable of using chloride ion as a substrate to form the highly microbicidal species hypochlorous acid (HOCl) at neutral pH. Despite the potent bacterial killing activity of HOCl, individuals who fail to express MPO typically show only a modest increase in some fungal infections. This may point to the existence of redundant host defense mechanisms. Vascular peroxidase 1 (VPO1) is newly discovered member of the heme peroxidase family. VPO1 is expressed in cells of the cardiovascular system and is secreted into the bloodstream. In the present study, we investigate whether VPO1 is capable of generating HOCl and its role in host defense. Like MPO, VPO1 in the presence of H2O2 and chloride generates HOC. VPO1-dependent HOC generation was demonstrated by chlorination of taurine and tyrosine using mass spectrometry. In addition, the VPO1/H2O2/Cl- system can cause the chlorination of monochlorodimedone and the oxidation of 5-thio-2-nitrobenzoic acid. Purified VPO1 and VPO1 in plasma mediate bacterial killing that is dependent on chloride and H2O2; killing is inhibited by peroxidase inhibitors and by the H2O2 scavenger catalase. In the presence of erythrocytes, bacterial killing by VPO1 is slightly reduced. Thus, VPO1, in addition to MPO, is the second member of the heme peroxidase family capable of generating HOCl under physiological conditions. VPO1 is likely to participate in host defense, with bactericidal activity mediated through the generation of HOCl.