CRTH2 plays an essential role in the pathophysiology of Cry j 1-induced pollinosis in mice
CRTH2 plays an essential role in the pathophysiology of Cry j 1-induced pollinosis in mice
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DOI：
10.4049/jimmunol.180.8.5680
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发表时间：
2008-04-15
影响因子：
4.4
通讯作者：
Nakamura, Masataka
中科院分区：
文献类型：
--
作者：
Nomiya, Rie;Okano, Mitsuhiro;Nakamura, Masataka
前列腺素D(2)是过敏反应急性期产生的主要前列腺素。目前已分离出两种PGD(2)受体，DP和CRTH2(Th2细胞上表达的趋化受体同源分子)，但它们是否参与变态反应性疾病的病理生理尚不清楚。我们研究了CRTH2在小鼠变应性鼻炎发病中的作用。首先，我们开发了一种新的小鼠花粉症模型，这是一种季节性变应性鼻炎。此外，还比较了野生型和CRTH2基因缺陷小鼠花粉症的病理生理学差异。同时观察CRTH2/T-前列腺素受体双拮抗剂雷马曲班的治疗作用。在没有佐剂的情况下，用柳杉花粉的主要变应原Cry j 1反复鼻腔致敏，可显著加重鼻部高反应性症状、Cry j 1特异性IgE和1gG1的产生、鼻腔嗜酸性粒细胞增多和Cry j 1诱导的颌下淋巴结细胞体外产生IL-4和IL-5。此外，Cry j1致敏小鼠鼻粘膜CRTH2基因表达显著升高。CRTH2基因缺陷小鼠反复鼻腔注射Cry j 1致敏后，其Cry j 1特异性IgE/IgG1的产生、鼻腔嗜酸性粒细胞增多和颌下淋巴结细胞产生IL-4的能力明显低于野生型小鼠。在雷马特班治疗的小鼠身上也发现了类似的结果。这些结果表明，致敏后PGD(2)-CRTH2的相互作用增强，并在变应性鼻炎，特别是花粉症的病理生理中起着促炎作用。
PGD(2) is the major prostanoid produced during the acute phase of allergic reactions. Two PGD(2) receptors have been isolated, DP and CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells), but whether they participate in the pathophysiology of allergic diseases remains unclear. We investigated the role of CRTH2 in the initiation of allergic rhinitis in mice. First, we developed a novel murine model of pollinosis, a type of seasonal allergic rhinitis. Additionally, pathophysiological differences in the pollinosis were compared between wild-type and CRTH2 gene-deficient mice. An effect of treatment with ramatroban, a CRTH2/T-prostanoid receptor dual antagonist, was also determined. Repeated intranasal sensitization with Cry j 1, the major allergen of Cryptomeria japonica pollen, in the absence of adjuvants significantly exacerbated nasal hyperresponsive symptoms, Cry j 1-specific IgE and 1gG1 production, nasal eosinophilia, and Cry j 1-induced in vitro production of IL-4 and IL-5 by submandibular lymph node cells. Additionally, CRTH2 mRNA in nasal mucosa was significantly elevated in Cry j 1-sensitized mice. Following repeated intranasal sensitization with Cry j 1, CRTH2 gene-deficient mice had significantly weaker Cry j 1-specific IgE/IgG1 production, nasal eosinophilia, and IL-4 production by submandibular lymph node cells than did wild-type mice. Similar results were found in mice treated with ramatroban. These results suggest that the PGD(2)- CRTH2 interaction is elevated following sensitization and plays a proinflammatory role in the pathophysiology of allergic rhinitis, especially pollinosis in mice.