Roles of of lipid mediators in inflammatory system

脂质介质在炎症系统中的作用

• 批准号: 14570100
• 负责人: YOKOMIZO Takehiko
• 金额: $ 2.56万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570100/
• 关键词: Leukotriene B4; BLT1; BLT2; Bronchial asthma; phospholipase

Functional leukotriene B4(LTB4) is expressed in mouse dendritic cells (DC) revealed by RT-PCR and chemotaxis assay. BTT1-null DC failed to produce IL-12, suggesting some roles of LTB4-BLT1 interaction in Th1 type responses. We also found that BLT1-deficient mice are resistant to airway hyperresponsiveness evoked by ovalbumin sensitization and inhalation. Eosinophil accumulation into bronchoalveolar fluid as well as Th2 cytokine accumulation were reduced in BLT1-deficient mice, suggesting important roles of BLT1 in Th2-type immune response and eosinophil recruitment to alveoli. BLT1 transfection into rat basophilic leukemia (RBL) cells caused potent degranulation upon LTB4 stimulation. This was blocked either by pretreatment of the cells with PTX, wortmannin, or depletion of extracellular calcium, suggesting the involvements of PI3Kinase gamma-dificient granulocytes failed to degranulate upon LTB4 stimulation.

RT-PCR和趋化实验表明，功能性白三烯B4(LTB4)在小鼠树突状细胞(DC)中表达。BTT1-空DC不能产生IL-12，提示LTB4-BLT1相互作用在Th1型应答中起一定作用。我们还发现，BLT1缺陷小鼠对卵蛋白敏化和吸入引起的呼吸道高反应性具有抵抗力。BLT1基因缺陷小鼠支气管肺泡液中嗜酸性粒细胞聚集减少，Th2细胞因子聚集减少，提示BLT1在Th2型免疫应答和嗜酸性粒细胞聚集到肺泡中起重要作用。将BLT1基因导入大鼠嗜碱性白血病(RBL)细胞，在LTB4刺激下可引起明显的脱颗粒现象。这可以通过PTX、Wortmannin或耗尽细胞外钙来阻断，这表明PI3Kinase伽玛缺乏的粒细胞在LTB4刺激下未能脱颗粒。

项目成果

Ogasawara, H., S.Ishii, T.Yokomizo, T.Kakinuma, M.Komine, K.Tamaki, T.Shimizu, T.Izumi: "Characterization of mouse cysteinyl leukotriene receptors mCysLT1 and mCysLT2: differential pharmacological properties and tissue distribution."J Biol Chem. 277(21).

Ogasawara, H., S.Ishii, T.Yokomizo, T.Kakinuma, M.Komine, K.Tamaki, T.Shimizu, T.Izumi：“小鼠半胱氨酰白三烯受体 mCysLT1 和 mCysLT2 的表征：不同的药理学特性和组织分布

Masuda, K., H.Itoh, T.Sakihama, C.Akiyama, K.Takahashi, R.Fukuda, T.Yokomizo, T.Shimizu, T.Kodama, T.Hamakubo: "A combinatorial G protein-coupled receptor reconstitution system on budded baculovirus. Evidence for Galpha and Galphao coupling to a human leu

Masuda, K., H.Itoh, T.Sakihama, C.Akiyama, K.Takahashi, R.Fukuda, T.Yokomizo, T.Shimizu, T.Kodama, T.Hamakubo：“组合 G 蛋白偶联受体重建

Yamauchi, T., J.Kamon, Y.Ito, A.Tsuchida, T.Yokomizo 他21名: "Cloning of adiponectin receptors that mediate antidiabetic metabolic effects."Nature. 423. 762-769 (2003)

Yamauchi, T., J.Kamon, Y.Ito, A.Tsuchida, T.Yokomizo 和其他 21 人：“介导抗糖尿病代谢作用的脂联素受体的克隆。”《自然》423. 762-769 (2003)

Yokomizo, T., E.Noiri, T.Izumi, T.Shimizu: "In vivo chemotaxis using CHO cells expressing human leukotriene B4 receptor."Adv Exp Med Biol. 507. 357-361 (2002)

Yokomizo, T.、E.Noiri、T.Izumi、T.Shimizu：“使用表达人白三烯 B4 受体的 CHO 细胞进行体内趋化性。”Adv Exp Med Biol。

Toda, A., T.Yokomizo, T.Shimizu: "Leukotriene B4 receptors."Prostaglandins Other Lipid Mediat. 68-69. 575-585 (2002)

Toda, A.、T.Yokomizo、T.Shimizu：“白三烯 B4 受体”。前列腺素其他脂质介质。