Upper Airways Research Laboratory, Department of Otorhinolaryngology, Ghent University Hospital, Ghent, Belgium.
Allergy. 2010 Mar;65(3):304-10. doi: 10.1111/j.1398-9995.2009.02204.x. Epub 2009 Oct 12.
Mast cells release mediators upon stimulation that contribute to the pathogenesis of chronic airway disease, including the recruitment and activation of Th2 lymphocytes. The objective was to determine the involvement of prostaglandin D(2) (PGD(2)) and its receptors in the chemotaxis of Th2 cells, using nasal polyp tissue.
Tissue explants from ten patients with nasal polyposis were incubated with RPMI alone or RPMI containing IgE/anti-IgE for 30 min. Some samples were treated with diclofenac to inhibit the production of PGD(2). Supernatants were assayed for PGD(2) content and for their ability to promote human Th2 cell chemotaxis in the presence and absence of a CRTH2 antagonist. Transcript levels of D protanoid receptor type 1 (DP(1)), chemoattractant receptor-homologous receptor expressed on Th2 cells (CRTH2) and PGD(2) synthase were analysed by real time PCR.
Increased release of PGD(2) by nasal polyp tissue treated with IgE/anti-IgE was significantly inhibited by preincubation of the tissue with diclofenac. Transcript levels of PGD(2) synthase, DP(1) and CRTH2 receptors increased after stimulation with IgE/anti-IgE. Supernatants from IgE/anti-IgE-stimulated nasal polyp tissue caused significantly increased chemotaxis of Th2 cells. The levels of PGD(2) produced and the degree of Th2 cell chemotaxis were highly correlated. Diclofenac inhibited the production of Th2 cell chemotactic activity, and the chemotactic effect of the supernatant on Th2 cells was inhibited by the CRTH2 antagonist ramatroban.
These data suggest that in immunologically activated nasal polyp tissue, PGD(2) produced by mast cells promotes the migration of Th2 cells through a CRTH2 dependent mechanism.
肥大细胞在受到刺激后会释放介质，这些介质有助于慢性气道疾病的发病机制，包括招募和激活 Th2 淋巴细胞。目的是使用鼻息肉组织确定前列腺素 D2（PGD2）及其受体在 Th2 细胞趋化中的作用。
用 RPMI 单独或含 IgE/抗 IgE 的 RPMI 孵育来自 10 名鼻息肉患者的组织外植体 30 分钟。一些样本用双氯芬酸处理以抑制 PGD2 的产生。检测上清液中 PGD2 的含量及其在存在和不存在 CRTH2 拮抗剂的情况下促进人 Th2 细胞趋化的能力。通过实时 PCR 分析 DP 型原啡烷受体 1（DP1）、嗜曙红细胞趋化因子同源受体表达于 Th2 细胞（CRTH2）和 PGD2 合酶的转录水平。
用 IgE/抗 IgE 处理的鼻息肉组织释放的 PGD2 明显增加，经双氯芬酸预孵育后明显抑制。用 IgE/抗 IgE 刺激后，PGD2 合酶、DP1 和 CRTH2 受体的转录水平增加。IgE/抗 IgE 刺激的鼻息肉组织上清液引起 Th2 细胞明显趋化。产生的 PGD2 水平和 Th2 细胞趋化程度高度相关。双氯芬酸抑制 Th2 细胞趋化活性的产生，CRTH2 拮抗剂 ramatroban 抑制上清液对 Th2 细胞的趋化作用。
这些数据表明，在免疫激活的鼻息肉组织中，肥大细胞产生的 PGD2 通过 CRTH2 依赖的机制促进 Th2 细胞的迁移。
