Roles of of lipid mediators in inflammatory system

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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.