Dual oxidases represent novel hydrogen peroxide sources supporting mucosal surface host defense
Dual oxidases represent novel hydrogen peroxide sources supporting mucosal surface host defense
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DOI：
10.1096/fj.02-1104fje
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发表时间：
2003-06-01
期刊：
影响因子：
4.8
通讯作者：
Leto, TL
中科院分区：
文献类型：
--
作者：
Geiszt, M;Witta, J;Leto, TL
乳过氧化物酶 (LPO) 是一种具有抗菌特性的酶，存在于唾液、牛奶、眼泪和气道分泌物中。尽管 LPO 形成微生物氧化剂的认识已有一段时间了，但 LPO 催化反应的过氧化氢 (H2O2) 来源仍然未知。吞噬细胞 NADPH 氧化酶 (phox) 产生的活性氧在宿主防御病原体方面发挥着关键作用；然而，其他组织中类似的氧化剂生成系统尚未与抗菌活性相关。最近描述了该酶的催化核心 gp91(phox) 的几种同系物；双氧化酶 (Duox)1/甲状腺氧化酶 1 和 Duox2/甲状腺氧化酶 2 在甲状腺中被鉴定，并被定性为甲状腺素生物合成的 H2O2 供体。我们检测了 Duox1 和 Duox2 在分泌腺和粘膜表面的表达，并提供了它们在唾液腺、直肠、气管和支气管中的存在和活性的证据。唾液排泄管和直肠腺中的上皮细胞表达 Duox2，而气管和支气管上皮细胞表达 Duox1。此外，我们检测到培养的人支气管上皮细胞依赖 Duox1 释放 H2O2。我们的观察表明，Duox1 和 Duox2 是新型 H2O2 来源，可以支持粘膜表面 LPO 介导的抗菌防御机制。
Lactoperoxidase (LPO) is an enzyme with antimicrobial properties present in saliva, milk, tears, and airway secretions. Although the formation of microbial oxidants by LPO has been recognized for some time, the source of hydrogen peroxide (H2O2) for LPO-catalyzed reactions remains unknown. Reactive oxygen species produced by the phagocyte NADPH oxidase (phox) play a critical role in host defense against pathogens; however, analogous oxidant-generating systems in other tissues have not been associated with antimicrobial activity. Several homologues of gp91(phox), the catalytic core of this enzyme, were described recently; dual oxidase (Duox)1/thyroid oxidase 1 and Duox2/thyroid oxidase 2 were identified in the thyroid gland and characterized as H2O2 donors for thyroxin biosynthesis. We examined Duox1 and Duox2 expression in secretory glands and on mucosal surfaces and give evidence for their presence and activity in salivary glands, rectum, trachea, and bronchium. Epithelium cells in salivary excretory ducts and rectal glands express Duox2, whereas tracheal and bronchial epithelial cells express Duox1. Furthermore, we detected Duox1-dependent H2O2 release by cultured human bronchial epithelial cells. Our observations suggest that Duox1 and Duox2 are novel H2O2 sources that can support LPO-mediated antimicrobial defense mechanisms on mucosal surfaces.