Prostaglandin D2 selectively induces chemotaxis in T helper type 2 cells, eosinophils, and basophils via seven-transmembrane receptor CRTH2.
Prostaglandin D2 selectively induces chemotaxis in T helper type 2 cells, eosinophils, and basophils via seven-transmembrane receptor CRTH2.
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DOI：
10.1084/jem.193.2.255
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发表时间：
2001-01-15
期刊：
影响因子：
--
通讯作者：
Nagata K
中科院分区：
文献类型：
--
作者：
Hirai H;Tanaka K;Yoshie O;Ogawa K;Kenmotsu K;Takamori Y;Ichimasa M;Sugamura K;Nakamura M;Takano S;Nagata K
前列腺素(PG)D2长期以来一直被认为与变态反应性疾病有关，目前被认为是通过DP受体(DP)诱导其生物学作用。最近在DP缺乏的小鼠身上证实了DP参与了过敏性哮喘的形成。然而，前列腺素D2的促炎作用不能仅用DP来解释。我们在这里展示了一个七跨膜受体CRTH2，它在人类的辅助性T细胞2型(Th2)细胞、嗜酸性粒细胞和嗜碱性粒细胞中优先表达，是PGD2的新受体。作为对PGD2的响应，CRTH2以GαI依赖的方式诱导Th2型细胞内钙离子的动员和趋化。此外，CRTH2，而不是DP，介导了血嗜酸性粒细胞和嗜碱性粒细胞依赖于PGD2的细胞迁移。因此，PGD2可能通过其双受体系统DP和CRTH2参与变态反应性炎症的多个方面。
Prostaglandin (PG)D2, which has long been implicated in allergic diseases, is currently considered to elicit its biological actions through the DP receptor (DP). Involvement of DP in the formation of allergic asthma was recently demonstrated with DP-deficient mice. However, proinflammatory functions of PGD2 cannot be explained by DP alone. We show here that a seven-transmembrane receptor, CRTH2, which is preferentially expressed in T helper type 2 (Th2) cells, eosinophils, and basophils in humans, serves as the novel receptor for PGD2. In response to PGD2, CRTH2 induces intracellular Ca2+ mobilization and chemotaxis in Th2 cells in a Gαi-dependent manner. In addition, CRTH2, but not DP, mediates PGD2-dependent cell migration of blood eosinophils and basophils. Thus, PGD2 is likely involved in multiple aspects of allergic inflammation through its dual receptor systems, DP and CRTH2.
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