Hirai H, Tanaka K, Yoshie O, Ogawa K, Kenmotsu K, Takamori Y, Ichimasa M, Sugamura K, Nakamura M, Takano S, Nagata K
R&D Center, BML, Saitama 350-1101, Japan.
J Exp Med. 2001 Jan 15;193(2):255-61. doi: 10.1084/jem.193.2.255.
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 Galphai-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.
长期以来，前列腺素（PG）D2一直被认为与过敏性疾病有关，目前认为它通过DP受体（DP）发挥其生物学作用。最近，在DP缺陷小鼠中证实了DP参与过敏性哮喘的形成。然而，PGD2的促炎功能不能仅由DP来解释。我们在此表明，一种七跨膜受体CRTH2，它在人类的2型辅助性T（Th2）细胞、嗜酸性粒细胞和嗜碱性粒细胞中优先表达，是PGD2的新型受体。响应PGD2时，CRTH2以依赖Galphai的方式在Th2细胞中诱导细胞内Ca2+动员和趋化性。此外，介导血液中嗜酸性粒细胞和嗜碱性粒细胞的PGD2依赖性细胞迁移的是CRTH2，而非DP。因此，PGD2可能通过其双受体系统DP和CRTH2参与过敏性炎症的多个方面。
