Prostaglandin D2 as a mediator of allergic asthma
Prostaglandin D2 as a mediator of allergic asthma
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DOI：
10.1126/science.287.5460.2013
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发表时间：
2000-03-17
期刊：
影响因子：
56.9
通讯作者：
Narumiya, S
中科院分区：
文献类型：
--
作者：
Matsuoka, T;Hirata, M;Narumiya, S
过敏性哮喘是由产生2型(T(H)2)细胞因子的辅助性T细胞在肺内异常扩张引起的，以嗜酸性粒细胞浸润和支气管高反应性为特征。这种疾病通常是由免疫球蛋白E(IgE)介导的过敏性攻击激活的肥大细胞引发的。激活的肥大细胞释放包括前列腺素D-2(PCD2)在内的各种化学介质，其在过敏性哮喘中的作用目前已通过PCD受体(DP)缺陷小鼠的生成来研究。卵蛋白(OVA)对纯合子突变(DP-/-)小鼠的致敏和气雾化激发可引起血清中IgE浓度的升高，与患此哮喘模型的野生型小鼠相似。然而，与野生型动物相比，OVA攻击的DP-/-小鼠T(H)2细胞因子的浓度和肺内淋巴细胞聚集的程度显著降低。此外，DP-/-小鼠仅表现出嗜酸性粒细胞的边缘渗透，并未出现呼吸道高反应性。因此，PGD(2)作为一种肥大细胞衍生的介质来触发哮喘反应。
Allergic asthma is caused by the aberrant expansion in the lung of T helper cells that produce type 2 (T(H)2) cytokines and is characterized by infiltration of eosinophils and bronchial hyperreactivity. This disease is often triggered by mast cells activated by immunoglobulin E (IgE)-mediated allergic challenge. Activated mast cells release Various chemical mediators, including prostaglandin D-2 (PCD2), whose role in allergic asthma has now been investigated by the generation of mice deficient in the PCD receptor (DP). Sensitization and aerosol challenge of the homozygous mutant (DP-/-) mice with ovalbumin (OVA) induced increases in the serum concentration of IgE similar to those in wild-type mice subjected to this model of asthma. However, the concentrations of T(H)2 cytokines and the extent of lymphocyte accumulation in the lung of OVA-challenged DP-/- mice were greatly reduced compared with those in wild-type animals. Moreover, DP-/- mice showed only marginal infiltration of eosinophils and failed to develop airway hyperreactivity. Thus, PGD(2) functions as a mast cell-derived mediator to trigger asthmatic responses.