Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Ann Allergy Asthma Immunol. 2011 Jun;106(6):511-7. doi: 10.1016/j.anai.2011.01.027. Epub 2011 Mar 21.
Prostaglandin D2 (PGD2) regulates various immunological responses via two distinct PGD2 receptors, prostaglandin D receptor (DP), and chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). Recent studies have demonstrated that PGD2 induces the migration of eosinophils through CRTH2. Although human eosinophils express both DP and CRTH2, it is unclear whether the function of DP is involved in eosinophil migration.
In this study, we investigated the roles of DP and CRTH2 in eosinophil migration by using selective agonists and antagonists.
Eosinophils were isolated from human subjects with mild eosinophilia by modified CD16-negative selection. After stimulation with or without DP receptor agonist, eosinophil migration was measured by Boyden chamber. The effect of DP agonists on CRTH2-induced eosinophil migration was studied in terms of CRTH2 expression, Ca2+ mobilization, ERK/MAPK phosphorylation, and cyclic AMP (cAMP) production.
Treatment with DP agonists inhibited CRTH2-induced chemotaxis of eosinophils. Furthermore, we showed that DP agonists enhanced cAMP production in CRTH2 agonist stimulation without increasing CRTH2 expression. DP mediates eosinophils through the elevation of intracellular cAMP production but does not change CRTH2 expression.
Taken together, the balance between DP and CRTH2 could influence the degree of PGD2-induced eosinophil migration and DP agonist might regulate eosinophil activation.
前列腺素 D2（PGD2）通过两种不同的 PGD2 受体，即前列腺素 D 受体（DP）和 Th2 细胞表达的趋化因子受体同源物（CRTH2），调节各种免疫反应。最近的研究表明，PGD2 通过 CRTH2 诱导嗜酸性粒细胞的迁移。尽管人嗜酸性粒细胞表达 DP 和 CRTH2，但 DP 的功能是否参与嗜酸性粒细胞的迁移尚不清楚。
本研究通过使用选择性激动剂和拮抗剂，探讨 DP 和 CRTH2 在嗜酸性粒细胞迁移中的作用。
通过改良的 CD16 阴性选择从轻度嗜酸性粒细胞增多症患者中分离嗜酸性粒细胞。用 DP 受体激动剂刺激或不刺激后，通过 Boyden 室测量嗜酸性粒细胞的迁移。研究 DP 激动剂对 CRTH2 诱导的嗜酸性粒细胞迁移的影响，包括 CRTH2 表达、Ca2+动员、ERK/MAPK 磷酸化和环磷酸腺苷（cAMP）产生。
DP 激动剂治疗抑制 CRTH2 诱导的嗜酸性粒细胞趋化作用。此外，我们表明 DP 激动剂在 CRTH2 激动剂刺激下增强 cAMP 的产生，而不增加 CRTH2 的表达。DP 通过升高细胞内 cAMP 的产生来介导嗜酸性粒细胞迁移，但不改变 CRTH2 的表达。
综上所述，DP 和 CRTH2 之间的平衡可能会影响 PGD2 诱导的嗜酸性粒细胞迁移的程度，DP 激动剂可能调节嗜酸性粒细胞的激活。
