Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
FASEB J. 2013 Aug;27(8):3306-14. doi: 10.1096/fj.12-217000. Epub 2013 Apr 19.
Leukotriene B4 (LTB4) has been implicated in the pathogenesis of allergic diseases. BLT2, a low-affinity LTB4 receptor, is activated by LTB4 and 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT). Although the high-affinity LTB4 receptor BLT1 has been shown to exert proinflammatory roles, the role of BLT2 in allergic inflammation has not been clarified. To study the function of BLT2 in development of asthma, we used mice model of ovalbumin (OVA)-induced allergic airway disease. The 12-HHT levels were elevated in bronchoalveolar lavage (BAL) fluids of OVA-sensitized/challenged wild-type mice. BLT2-deficient mice exhibited enhanced eosinophilia in BAL fluids after OVA exposure. Interleukin (IL)-13 levels in BAL fluids and IL-13-producing CD4(+) T cells in the lungs were elevated in BLT2-deficient mice compared to wild-type mice, whereas the levels of IL-4, IL-5, and interferon (IFN)-γ in BAL fluids and serum OVA-specific IgE were comparable. Transfection of BLT2-specific small interfering RNA enhanced IL-13 production in CD4(+) T cells in vitro. Expression of BLT2 mRNA in CD4(+) T cells was significantly reduced in patients with asthma compared to healthy control subjects. These findings indicate that BLT2 has a protective role in allergic airway inflammation and that diminished BLT2 expression in CD4(+) T cells may contribute to the pathophysiology of asthma.
白三烯 B4（LTB4）与过敏疾病的发病机制有关。BLT2 是一种低亲和力的 LTB4 受体，可被 LTB4 和 12(S)-羟基十七碳-5Z,8E,10E-三烯酸（12-HHT）激活。虽然高亲和力的 LTB4 受体 BLT1 已被证明具有促炎作用，但 BLT2 在过敏炎症中的作用尚未阐明。为了研究 BLT2 在哮喘发展中的作用，我们使用卵清蛋白（OVA）诱导的过敏性气道疾病小鼠模型。OVA 致敏/激发的野生型小鼠的支气管肺泡灌洗液（BAL）中，12-HHT 水平升高。BLT2 缺陷型小鼠在暴露于 OVA 后 BAL 液中的嗜酸性粒细胞增多。与野生型小鼠相比，BLT2 缺陷型小鼠的 BAL 液中白细胞介素（IL）-13 水平和肺部产生 IL-13 的 CD4(+)T 细胞升高，而 BAL 液中 IL-4、IL-5 和干扰素（IFN）-γ 以及血清 OVA 特异性 IgE 水平相当。BLT2 特异性小干扰 RNA 的转染增强了 CD4(+)T 细胞中 IL-13 的产生。与健康对照组相比，哮喘患者 CD4(+)T 细胞中 BLT2 mRNA 的表达明显降低。这些发现表明 BLT2 在过敏性气道炎症中具有保护作用，而 CD4(+)T 细胞中 BLT2 表达的减少可能导致哮喘的病理生理学。
