Honda Kyoko, Arima Masafumi, Cheng Gang, Taki Shinsuke, Hirata Hirokuni, Eda Fukiko, Fukushima Fumiya, Yamaguchi Bunpei, Hatano Masahiko, Tokuhisa Takeshi, Fukuda Takeshi
Deptartment of Pulmonary Medicine and Clinical Immunology, Dokkyo University School of Medicine, Mibu-machi Shimotsuga-gun, Tochigi 321-0293, Japan.
J Exp Med. 2003 Aug 18;198(4):533-43. doi: 10.1084/jem.20022218.
PGD2, a lipid mediator released from mast cells, is known to participate in allergic reactions. However, the mechanism by which PGD2 contributes to such reactions remains unclear. We established a novel experimental model of asthma that permitted direct assessment of the role of PGD2 in airway inflammation. Antigen-sensitized mice were exposed to aerosolized prostaglandin D2 (PGD2) 1 d before challenge with low-dose aerosolized antigen. Not only the numbers of eosinophils, lymphocytes, and macrophages but also the levels of IL-4 and IL-5 in bronchoalveolar lavage fluid were higher in PGD2-pretreated mice than in control mice. The expression of macrophage-derived chemokine (MDC), a chemoattractant for Th2 cells, was greater in PGD2-pretreated mice than in control. Injection of anti-MDC antibody into PGD2-pretreated mice markedly inhibited inflammatory cell infiltration as well as Th2 cyto-kine production after antigen challenge. These results indicate that PGD2 accelerates Th2 type inflammation by induction of MDC. Our results suggest that this mechanism may play a key role in the development of human asthma and that MDC might be a target molecule for therapeutic intervention.
前列腺素D2（PGD2）是一种从肥大细胞释放的脂质介质，已知其参与过敏反应。然而，PGD2促成此类反应的机制仍不清楚。我们建立了一种新型哮喘实验模型，可直接评估PGD2在气道炎症中的作用。在低剂量雾化抗原激发前1天，将抗原致敏小鼠暴露于雾化的前列腺素D2（PGD2）。与对照小鼠相比，PGD2预处理小鼠支气管肺泡灌洗液中的嗜酸性粒细胞、淋巴细胞和巨噬细胞数量以及IL-4和IL-5水平更高。巨噬细胞衍生趋化因子（MDC，一种Th2细胞趋化因子）在PGD2预处理小鼠中的表达高于对照。向PGD2预处理小鼠注射抗MDC抗体可显著抑制抗原激发后炎症细胞浸润以及Th2细胞因子产生。这些结果表明，PGD2通过诱导MDC加速Th2型炎症。我们的结果表明，这一机制可能在人类哮喘的发展中起关键作用，并且MDC可能是治疗干预的靶分子。
