Shin Eun Ha, Lee Ha Young, Bae Yoe-Sik
Medical Research Center for Cancer Molecular Therapy and Department of Biochemistry, College of Medicine, Dong-A University, Busan 602-714, Republic of Korea.
Biochem Biophys Res Commun. 2006 Sep 22;348(2):606-11. doi: 10.1016/j.bbrc.2006.07.084. Epub 2006 Jul 28.
Although leukotriene B4 (LTB4) has been reported to stimulate monocytes and neutrophils, its role on dendritic cell (DC) activity has not been examined. Here, we investigated the expression of LTB4 receptor and the effect of LTB4 on human DC chemotaxis. We analyzed LTB4 receptors, BLT1 and BLT2, by using RT-PCR. DCs express BLT2 but not BLT1 mRNA. DCs were chemotactically migrated to LTB4. LTB4-induced DC chemotaxis was completely inhibited by pertussis toxin, indicating the role of Gi proteins. LTB4 induced mitogen activated protein kinase activation and Akt activation. LTB4-induced DC chemotaxis was mediated by extracellular signal-regulated protein kinase and phosphoinositide 3-kinase but not by p38 kinase. BLT2-selevite antagonist, LY255283, almost completely inhibited DC chemotaxis induced by LTB4 but not by Trp-Lys-Tyr-Met-Val-D-Met. Thus human myeloid DCs express functional BLT2 but not BLT1, suggesting a physiological role of LTB4 and BLT2 in regulating DC trafficking during induction of immune responses.
尽管据报道白三烯B4(LTB4)可刺激单核细胞和中性粒细胞,但其对树突状细胞(DC)活性的作用尚未得到研究。在此,我们研究了LTB4受体的表达以及LTB4对人DC趋化性的影响。我们使用逆转录聚合酶链反应(RT-PCR)分析了LTB4受体BLT1和BLT2。DC表达BLT2 mRNA但不表达BLT1 mRNA。DC可通过趋化作用迁移至LTB4。百日咳毒素可完全抑制LTB4诱导的DC趋化作用,表明Gi蛋白发挥了作用。LTB4可诱导丝裂原活化蛋白激酶激活和Akt激活。LTB4诱导的DC趋化作用是由细胞外信号调节蛋白激酶和磷酸肌醇3激酶介导的,而非由p38激酶介导。BLT2选择性拮抗剂LY255283几乎完全抑制LTB4诱导的DC趋化作用,但不抑制色氨酸-赖氨酸-酪氨酸-蛋氨酸-缬氨酸-D-蛋氨酸诱导的DC趋化作用。因此,人髓样DC表达功能性BLT2而非BLT1,提示LTB4和BLT2在免疫应答诱导过程中调节DC迁移方面具有生理作用。