Prostaglandin D2 reinforces Th2 type inflammatory responses of airways to low-dose antigen through bronchial expression of macrophage-derived chemokine.
Prostaglandin D2 reinforces Th2 type inflammatory responses of airways to low-dose antigen through bronchial expression of macrophage-derived chemokine.
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DOI：
10.1084/jem.20022218
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发表时间：
2003-08-18
期刊：
影响因子：
--
通讯作者：
Fukuda T
中科院分区：
文献类型：
--
作者：
Honda K;Arima M;Cheng G;Taki S;Hirata H;Eda F;Fukushima F;Yamaguchi B;Hatano M;Tokuhisa T;Fukuda T
已知PGD 2是肥大细胞释放的脂质介质，参与过敏反应。然而，PGD 2促进这些反应的机制仍不清楚。我们建立了一种新的哮喘实验模型，可以直接评估PGD 2在气道炎症中的作用。抗原致敏小鼠暴露于雾化前列腺素D2（PGD 2）1天前的挑战与低剂量雾化抗原。PGD 2预处理小鼠支气管肺泡灌洗液中嗜酸性粒细胞、淋巴细胞和巨噬细胞的数量以及IL-4和IL-5的水平均高于对照小鼠。巨噬细胞源性趋化因子（MDC），一种Th 2细胞的趋化因子，在PGD 2预处理的小鼠中的表达高于对照组。给PGD_2预处理的小鼠注射抗MDC抗体可明显抑制抗原攻击后的炎性细胞浸润和Th_2细胞因子的产生。这些结果表明，PGD 2通过诱导MDC加速Th 2型炎症。我们的研究结果表明，这种机制可能在人类哮喘的发展中起着关键作用，MDC可能是治疗干预的靶分子。
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.
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DOI：
10.1164/rccm.2105079
发表时间：
2002-08-01
影响因子：
24.7
作者：
Cheng, G;Arima, M;Fukuda, T
通讯作者：
Fukuda, T
影响因子：
7.3
作者：
FLOWER, RJ;HARVEY, EA;KINGSTON, WP
通讯作者：
KINGSTON, WP
DOI：
10.1164/ajrccm.156.3.9606031
发表时间：
1997-09-01
影响因子：
24.7
作者：
Hamelmann, E;Schwarze, J;Gelfand, EW
通讯作者：
Gelfand, EW
影响因子：
4.4
作者：
Fujitani, Y;Kanaoka, Y;Urade, Y
通讯作者：
Urade, Y
影响因子：
15.3
作者：
Bonecchi, R;Bianchi, G;Bordignon, P P;D'Ambrosio, D;Lang, R;Borsatti, A;Sozzani, S;Allavena, P;Gray, P A;Mantovani, A;Sinigaglia, F
通讯作者：
Sinigaglia, F