Dermal nitrite application enhances global nitric oxide availability: new therapeutic potential for immunomodulation?
Dermal nitrite application enhances global nitric oxide availability: new therapeutic potential for immunomodulation?
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皮肤亚硝酸盐应用增强了全球一氧化氮的可用性：免疫调节的新治疗潜力？
DOI：
10.1038/jid.2009.303
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Feelisch,Martin
中科院分区：
文献类型：
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作者：
Garcia-Saura,MariaFrancisca;Fernandez,BernadetteO;McAllister,BrianP;Whitlock,DavidR;Cruikshank,WilliamW;Feelisch,Martin
皮肤中或皮肤上的亚硝酸盐具有强大的抗菌作用，被认为是局部一氧化氮(NO)的储存库，能够调节皮肤细胞的功能。我们在这里用雄性Wistar大鼠证明，当亚硝酸盐在中性水溶液中应用于皮肤表面时，很容易渗透到真皮，到达体循环，并引起组织蛋白的广泛亚硝化。这些事件延伸到所有被调查的内脏，包括对免疫细胞功能的调节至关重要的部分，如胸腺、脾和淋巴结。利用过敏性哮喘的转基因小鼠模型，我们进一步发现，全身给予亚硝酸盐可以有效地抑制T细胞和其他炎症细胞的数量，以及Th2效应细胞因子IL-13的产生。因此，通过还原硝酸盐或皮肤上的氨氧化形成的亚硝酸盐，可能会产生类似于NO的以前未被意识到的全身性影响。这些观察结果有可能将目前亚硝酸盐的重点从心血管药理学转移到免疫学。
Nitrite in/on the skin has potent antimicrobial effects and is believed to act as a local nitric oxide (NO) reservoir capable of modulating dermal cell function. Using male Wistar rats we here show that nitrite, when applied in neutral aqueous solution to the skin surface, readily permeates the dermis to reach the systemic circulation and cause widespread nitros (yl) ation of tissue proteins. These events extend to all internal organs investigated including compartments crucial for the regulation of immune cell function such as thymus, spleen and lymph nodes. Using a transgenic mouse model of allergic asthma, we further find that systemic nitrite administration potently suppresses the number of T-cells and other inflammatory cells and the production of the Th2 effector cytokine, IL-13 in the lung. Thus, nitrite formed via reduction of nitrate or oxidation of ammonia on the skin, may exert previously unappreciated systemic effects akin to NO. These observations have the potential to shift the current emphasis of nitrite from cardiovascular pharmacology to immunology.