An α4β1 integrin antagonist decreases airway inflammation in ovalbumin-exposed mice
An α4β1 integrin antagonist decreases airway inflammation in ovalbumin-exposed mice
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DOI：
10.1016/j.ejphar.2008.11.063
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发表时间：
2009-01-28
影响因子：
5
通讯作者：
Lam, Kit S.
中科院分区：
文献类型：
--
作者：
Kenyon, Nicholas J.;Liu, Ruiwu;Lam, Kit S.
在各种动物模型中，α 4 β 1和α 4 β 7整联蛋白的α 4亚基的抑制已显示出降低气道炎症和气道高反应性的前景。我们假设，一种新型的，高亲和力的α 4 β 1拮抗剂（LLP 2A）将减少嗜酸性粒细胞迁移到肺，并改善小鼠模型的卵清蛋白诱导的气道炎症的气道高反应性。为了验证这一假设，我们在致敏BALB/c小鼠暴露于卵清蛋白气雾剂之前给予LLP 2A或混杂LLP 2A（阴性对照）。我们可以部分预防或逆转气道炎症反应，但不能气道高反应性，通过用LLP 2A，一种合成的肽模拟物α 4 β 1拮抗剂治疗小鼠。这种拮抗剂的特别工程化的PEG化的（PEG）制剂进一步减少对卵清蛋白的气道炎症反应，推测是通过改善药物的循环半衰期。(C)2008 Elsevier B. V.保留所有权利。
Inhibition of the alpha 4 subunit of both the alpha 4 beta 1 and alpha 4 beta 7 integrins has shown promise in decreasing airway inflammation and airway hyperresponsiveness in various animal models. We hypothesized that a novel, high-affinity alpha 4 beta 1 antagonist (LLP2A) would decrease the migration of eosinophils to the lung and ameliorate the airway hyperresponsiveness in a mouse model of ovalbumin-induced airway inflammation. To test this hypothesis, we administered LLP2A, or scrambled LLP2A (a negative control), prior to exposure of sensitized BALB/c mice to ovalbumin aerosol. We can partially prevent, or reverse, the airway inflammatory response, but not airways hyperresponsiveness, by treatment of mice with LLP2A, a synthetic peptidomimetic alpha 4 beta 1 antagonist. Specifically engineered, PEGylatecl (PEG) formulations of this antagonist further reduce the airway inflammatory response to ovalbumin, presumably by improving the circulating half-life of the drug. (C) 2008 Elsevier B.V. All rights reserved.