Multi-pronged inhibition of airway hyper-responsiveness and inflammation by lipoxin A4
Multi-pronged inhibition of airway hyper-responsiveness and inflammation by lipoxin A4
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DOI：
10.1038/nm748
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发表时间：
2002-09-01
期刊：
影响因子：
82.9
通讯作者：
Serhan, CN
中科院分区：
文献类型：
--
作者：
Levy, BD;DeSanctis, GT;Serhan, CN
哮喘的患病率继续增加，其最佳治疗仍然是一个挑战。在此，我们使用哮喘小鼠模型研究了脂氧素A（4）（LXA（4））及其白细胞受体在肺部炎症中的作用。过敏原刺激启动LXA（4）的气道生物合成，并增加其受体的表达。给予LXA的稳定类似物（4）可阻断气道高反应性和肺部炎症，如白细胞和介质（包括白细胞介素-5、白细胞介素-13、嗜酸性粒细胞趋化因子、前列腺素和半胱氨酰白三烯）减少所示。此外，在小鼠白细胞中转基因表达人LXA（4）受体导致肺部炎症和类花生酸引发的嗜酸性粒细胞组织浸润的显着抑制。用稳定的LXA（4）类似物抑制气道高反应性和过敏性气道炎症突出了LXA（4）系统及其白细胞受体在气道反应中的独特反调节特征。此外，我们的研究结果表明，脂氧素和相关途径为人类哮喘提供了新的多管齐下的治疗方法。
The prevalence of asthma continues to increase and its optimal treatment remains a challenge. Here, we investigated the actions of lipoxin A(4) (LXA(4)) and its leukocyte receptor in pulmonary inflammation using a murine model of asthma. Allergen challenge initiated airway biosynthesis of LXA(4) and increased expression of its receptor. Administration of a stable analog of LXA(4) blocked both airway hyper-responsiveness and pulmonary inflammation, as shown by decreased leukocytes and mediators, including interleukin-5, interleukin-13, eotaxin, prostanoids and cysteinyl leukotrienes. Moreover, transgenic expression of human LXA(4) receptors in murine leukocytes led to significant inhibition of pulmonary inflammation and eicosanoid-initiated eosinophil tissue infiltration. Inhibition of airway hyper-responsiveness and allergic airway inflammation with a stable LXA(4) analog highlights a unique counter-regulatory profile for the LXA(4) system and its leukocyte receptor in airway responses. Moreover, our findings suggest that lipoxin and related pathways offer novel multi-pronged therapeutic approaches for human asthma.