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首页> 外文期刊>The journal of immunology >Nonredundant Roles for Leukotriene B4 Receptors BLT1 and BLT2 in Inflammatory Arthritis
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Nonredundant Roles for Leukotriene B4 Receptors BLT1 and BLT2 in Inflammatory Arthritis

机译：白三烯B4受体BLT1和BLT2在炎性关节炎中的非冗余作用

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Lipid mediators derived from arachidonic acid through the cyclooxygenase and lipoxygenase pathways are known to be important mediators of inflammation. Studies in mouse models demonstrated an important role for the high-affinity leukotriene B4 receptor BLT1 in arthritis, atherosclerosis, and asthma. BLT2, a low-affinity leukotriene B4 receptor, was also shown to be a high-affinity receptor for cyclooxygenase-1 derived 12(S)-hydroxyheptadeca-5Z, 8E, 10E-trienoic acid. However, its biochemical activities and physiological roles remain unknown. In this study, we developed mice deficient in BLT2 by targeted disruption. The BLT2?/? mice developed normally, and analysis of immune cells showed that disruption of BLT2 did not alter BLT1 expression or function. Mast cells from the C57BL/6 mice but not from the BLT2?/? mice showed intracellular calcium mobilization in response to 12(S)-hydroxyheptadeca-5Z, 8E, 10E-trienoic acid. In an autoantibody-induced inflammatory arthritis model, the BLT2?/? mice showed reduced incidence and severity of disease, including protection from bone and cartilage loss. Reciprocal bone marrow transplant experiments identified that loss of BLT2 expression on a bone marrow-derived cell lineage offers protection against severe disease. Thus, BLT2, a unique receptor for 5-lipoxygenase– and cyclooxygenase-1–derived lipid mediators, represents a novel target for therapies directed at treating inflammation associated with arthritis.
机译：已知通过环氧合酶和脂氧合酶途径从花生四烯酸衍生的脂质介体是炎症的重要介体。小鼠模型研究证明，高亲和力白三烯B4受体BLT1在关节炎，动脉粥样硬化和哮喘中具有重要作用。 BLT2，一种低亲和力的白三烯B4受体，也被证明是环氧合酶-1衍生的12（S）-hydroxyheptadeca-5Z，8E，10E-三烯酸的一种高亲和力受体。但是，其生化活性和生理作用仍然未知。在这项研究中，我们通过靶向破坏开发了BLT2缺陷的小鼠。 BLT2？/？小鼠正常发育，对免疫细胞的分析表明，破坏BLT2不会改变BLT1的表达或功能。来自C57BL / 6小鼠的肥大细胞，但不是来自BLT2α/β的肥大细胞。小鼠显示出对12（S）-hydroxyheptadeca-5Z，8E，10E-三烯酸的细胞内钙动员。在自身抗体诱导的炎性关节炎模型中，BLT2α/β是由BLT2α/β组成的。小鼠显示出疾病的发生率和严重性降低，包括防止骨骼和软骨丢失。相互进行的骨髓移植实验确定，骨髓来源的细胞谱系中BLT2表达的丧失可提供对严重疾病的保护。因此，BLT2是5-脂氧合酶和环氧合酶-1衍生的脂质介体的独特受体，代表了针对治疗与关节炎相关的炎症的新型靶标。

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