Pronounced eosinophilic lung inflammation and Th2 cytokine release in human lipocalin-type prostaglandin D synthase transgenic mice
Pronounced eosinophilic lung inflammation and Th2 cytokine release in human lipocalin-type prostaglandin D synthase transgenic mice
复制标题
DOI：
10.4049/jimmunol.168.1.443
复制
发表时间：
2002-01-01
影响因子：
4.4
通讯作者：
Urade, Y
中科院分区：
文献类型：
--
作者：
Fujitani, Y;Kanaoka, Y;Urade, Y
PGD（2）是肥大细胞释放的主要脂质介质，但对其在过敏反应发生中的作用知之甚少。我们使用过表达人脂质运载蛋白型PGD合酶的转基因（TG）小鼠来检测在OVA诱导的小鼠哮喘模型中PGD（2）过量产生的影响。野生型（WT）和TG小鼠的致敏性是相似的，判断的OVA特异性IgE的含量。在卵清蛋白攻击后，WT和TG小鼠肺中PGD（2）而不是PGE（2）显著增加，与WT小鼠相比，TG小鼠中PGD（2）增加更大。在OVA激发后第1天和第3天，TG小鼠支气管肺泡灌洗液（BAL）中嗜酸性粒细胞和淋巴细胞的数量显著高于WT小鼠，而WT和TG小鼠中巨噬细胞和中性粒细胞的数量相同。尽管TG小鼠的BAL液中IFN-γ的水平与WT小鼠相比降低，但TG小鼠的BAL液中IL-4、IL-5和嗜酸性粒细胞趋化因子的水平也显著高于WT小鼠。此外，从TG小鼠肺中分离的淋巴细胞分泌的IFN-γ比WT小鼠少，而IL-4的产生在WT和TG小鼠之间没有变化。因此，PGD（2）的过度产生导致Th 2细胞因子和趋化因子水平的增加，伴随着肺中嗜酸性粒细胞和淋巴细胞的积聚增加。提示PGD（2）在支气管哮喘的病理生理学中，在迟发相变态反应中起重要作用。
PGD(2) is a major lipid mediator released from mast cells, but little is known about its role in the development of allergic reactions. We used transgenic (TG) mice overexpressing human lipocalin-type PGD synthase to examine the effect of overproduction of PGD(2) in an OVA-induced murine asthma model. The sensitization of wild-type (WT) and TG mice was similar as judged by the content of OVA-specific IgE. After OVA challenge, PGD(2), but not PGE(2), substantially increased in the lungs of WT and TG mice with greater PGD(2) increment in TG mice compared with WT mice. The numbers of eosinophils and lymphocytes in the bronchoalveolar lavage (BAL) fluid were significantly greater in TG mice than in WT mice on days 1 and 3 post-OVA challenge, whereas the numbers of macrophages and neutrophils were the same in both WT and TG mice. The levels of IL-4, IL-5, and eotaxin in BAL fluid were also significantly higher in TG mice than in WT mice, although the level of IFN-gamma in the BAL fluid of TG mice was decreased compared with that in WT mice. Furthermore, lymphocytes isolated from the lungs of TG mice secreted less IFN-gamma than those from WT mice, whereas IL-4 production was unchanged between WT and TG mice. Thus, overproduction of PGD(2) caused an increase in the levels of Th2 cytokines and a chemokine, accompanied by the enhanced accumulation of eosinophils and lymphocytes in the lung. These results indicate that PGD(2) plays an important role in late phase allergic reactions in the pathophysiology of bronchial asthma.