Topically applied nitric oxide induces T-Lymphocyte infiltration in human skin, but minimal inflammation
Topically applied nitric oxide induces T-Lymphocyte infiltration in human skin, but minimal inflammation
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DOI：
10.1038/sj.jid.5701096
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发表时间：
2008-02-01
影响因子：
6.5
通讯作者：
Weller, Richard B.
中科院分区：
文献类型：
--
作者：
Mowbray, Megan;Tan, Xuejing;Weller, Richard B.
一氧化氮（NO）在皮肤对紫外线辐射的反应和皮肤炎症中起着重要作用。在许多炎症性皮肤病中存在可诱导的NO合成酶蛋白，加上局部应用NO供体酸化亚硝酸盐（NO2-）后诱导强烈的皮肤炎症浸润，已经树立了NO作为人类皮肤炎症介质的典范。使用沸石NO (Ze-NO)，一种化学惰性，纯NO供体，我们已经证明NO本身产生很少的炎症。生物学上，相关剂量的Ze-NO诱导真皮cd4阳性t细胞浸润和ifn - γ分泌。相反，酸化亚硝酸盐，释放等量的NO（通过皮肤微透析和皮肤红斑测量），诱导巨噬细胞强烈的表皮浸润，与CD3-， CD4-， CD8-和cd68阳性细胞和中性粒细胞的皮肤浸润相似。在ze - no处理皮肤和对照皮肤中产生抽吸泡。在ze - no处理的皮肤中检测到ifn - γ，但未检测到IL-4（对照组平均0.1 +/- 0.07 pgmg（-1）蛋白，平均IFN-g 0.670.4 pgmg（-1）蛋白）。我们认为酸化NO2-诱导的强效炎症是继发于其他介质的释放。
Nitric oxide (NO) plays an important role in the cutaneous response to UV radiation and in cutaneous inflammation. The presence of inducible NO synthase protein in a number of inflammatory dermatoses, coupled with the induction of an intense cutaneous inflammatory infiltrate following topical application of the NO donor-acidified nitrite (NO2-), has set the paradigm of NO being an inflammatory mediator in human skin. Using zeolite NO (Ze-NO), a chemically inert, pure NO donor, we have shown that NO per se produces little inflammation. Biologically, relevant doses of Ze-NO induce a dermal CD4-positive T-cell infiltrate and IFN-gamma secretion. In contrast acidified nitrite, releasing equal quantities of NO (measured by dermal microdialysis and cutaneous erythema), induces an intense epidermal infiltrate of macrophages with a similar dermal infiltrate of CD3-, CD4-, CD8-, and CD68-positive cells and neutrophils. Suction blisters were created in Ze-NO-treated and control skin. IFN-gamma, but not IL-4, was detected in Ze-NO-treated skin (mean control 0.1 +/- 0.07 pg mg(-1) protein, mean IFN-g 0.670.4 pgmg(-1) protein). We suggest that the potent inflammation induced by acidified NO2- is secondary to the release of additional mediators.