Shirasaki Hideaki, Kikuchi Megumi, Kanaizumi Etsuko, Himi Tetsuo
Department of Otolaryngology, Sapporo Medical University, School of Medicine, Sapporo, Japan.
Ann Allergy Asthma Immunol. 2009 Feb;102(2):110-5. doi: 10.1016/S1081-1206(10)60239-6.
Prostaglandin D2 (PGD2) has been thought to be a potent mediator involved in allergic rhinitis because PGD2 has been recovered from the nasal lavage fluid of patients with allergic rhinitis after allergen provocation and because PGD2 receptor antagonists relieved nasal allergic symptoms in an animal model of allergic rhinitis. The inflammatory effects of PGD2 are exerted through high-affinity interactions with 2 G protein-coupled receptors: D-prostanoid receptor 1 and chemoattractant-homologous receptor expressed on TH2 cells (CRTH2). CRTH2 may mediate the recruitment of leukocytes during a nasal allergic response.
To evaluate the number of CRTH2-expressing cells in allergic and nonallergic human nasal mucosa by means of immunohistochemical analysis.
Human turbinates were obtained after turbinectomy from 14 patients with nasal obstruction refractory to medical therapy. To identify cells expressing the CRTH2 protein, double immunostaining was performed using anti-CRTH2 antibody and monoclonal anti-leukocyte antibodies.
The immunohistochemical study revealed that anti-CRTH2 antibody labeled eosinophils, macrophages, mast cells, T lymphocytes, epithelial cells, and submucosal glands in the nasal mucosa. CRTH2 expressions of these leukocytes in allergic nasal mucosa are significantly up-regulated compared with those in nonallergic nasal mucosa.
These results suggest that CRTH2 may play an important role in the recruitment of leukocytes into allergic nasal mucosa.
前列腺素D2(PGD2)被认为是参与变应性鼻炎的一种强效介质,这是因为在变应原激发后从变应性鼻炎患者的鼻腔灌洗液中检测到了PGD2,还因为PGD2受体拮抗剂在变应性鼻炎动物模型中可缓解鼻部变应性症状。PGD2的炎症效应是通过与2种G蛋白偶联受体的高亲和力相互作用发挥的:D-前列腺素受体1和在TH2细胞上表达的趋化因子同源受体(CRTH2)。CRTH2可能在鼻部变应性反应期间介导白细胞的募集。
通过免疫组织化学分析评估变应性和非变应性人鼻黏膜中表达CRTH2的细胞数量。
从14例药物治疗无效的鼻塞患者行鼻甲切除术后获取人鼻甲。为鉴定表达CRTH2蛋白的细胞,使用抗CRTH2抗体和单克隆抗白细胞抗体进行双重免疫染色。
免疫组织化学研究显示,抗CRTH2抗体标记了鼻黏膜中的嗜酸性粒细胞、巨噬细胞、肥大细胞、T淋巴细胞、上皮细胞和黏膜下腺。与非变应性鼻黏膜相比,变应性鼻黏膜中这些白细胞的CRTH2表达显著上调。
这些结果提示,CRTH2可能在白细胞募集到变应性鼻黏膜过程中起重要作用。