Myeloperoxidase, a leukocyte-derived vascular NO oxidase
Myeloperoxidase, a leukocyte-derived vascular NO oxidase
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DOI：
10.1126/science.1106830
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发表时间：
2002-06-28
期刊：
影响因子：
56.9
通讯作者：
Freeman, BA
中科院分区：
文献类型：
--
作者：
Eiserich, JP;Baldus, S;Freeman, BA
髓过氧化物酶(MPO)是一种丰富的哺乳动物吞噬细胞血蛋白，被认为主要介导宿主防御反应。虽然它的杀菌功能在体外得到了很好的证实，但MPO缺陷的人不会面临异常的感染风险。在急性炎症过程中，观察MPO对一氧化氮(NO)的血管信号和血管扩张功能的调节作用。在白细胞脱颗粒后，在急性内毒素血症的啮齿动物模型中，MPO定位于血管内皮细胞及其周围，并损害内皮依赖性的松弛反应，而MPO缺陷小鼠对此具有抵抗力。血管反应性的改变是由于MPO产生的底物自由基催化消耗NO所致。因此，MPO可以通过调节NO的生物利用度直接调节血管炎症反应。
Myeloperoxidase (MPO) is an abundant mammalian phagocyte hemoprotein thought to primarily mediate host defense reactions. Although its microbicidal functions are well established in vitro, humans deficient in MPO are not at unusual risk of infection. MPO was observed herein to modulate the vascular signaling and vasodilatory functions of nitric oxide (NO) during acute inflammation. After leukocyte degranulation, MPO localized in and around vascular endothelial cells in a rodent model of acute endotoxemia and impaired endothelium-dependent relaxant responses, to which MPO-deficient mice were resistant. Altered vascular responsiveness was due to catalytic consumption of NO by substrate radicals generated by MPO. Thus MPO can directly modulate vascular inflammatory responses by regulating NO bioavailability.