Role of ABCO in export of sphingosine-1-phosphate from mast cells
Role of ABCO in export of sphingosine-1-phosphate from mast cells
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DOI：
10.1073/pnas.0603734103
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发表时间：
2006-10-31
影响因子：
11.1
通讯作者：
Spiegel, Sarah
中科院分区：
文献类型：
--
作者：
Mitra, Poulami;Oskeritzian, Carole A.;Spiegel, Sarah
肥大细胞通过分泌多种强效炎症介质，包括鞘氨醇-1-磷酸（S1P），在炎症和即时型过敏反应中发挥关键作用。然而，尚不清楚S1P是如何从细胞中释放出来的。在这里，我们报道了S1P独立于肥大细胞的脱颗粒而从肥大细胞中输出，并证明它是由ATP结合盒（ABC）转运蛋白介导的。ABCC1 （MRP1）抑制剂MK571抑制构成型和抗原刺激的S1P释放，但ABCb1 （MDR-1， p -糖蛋白）抑制剂不抑制S1P释放。此外，用小干扰RNA下调ABCC1，降低其细胞表面表达，显著减少大鼠RBL-2H3和人LAD2肥大细胞的S1P输出。abcc1转运S1P影响肥大细胞向抗原的迁移，但不影响脱颗粒。这些发现对S1P在肥大细胞介导的免疫应答中的功能具有重要意义。
Mast cells play a pivotal role in inflammatory and immediate-type allergic reactions by secreting a variety of potent inflammatory mediators, including sphingosine-1-phosphate (S1P). However, it is not known how S1P is released from cells. Here, we report that S1P is exported from mast cells independently of their degranulation and demonstrate that it is mediated by ATP binding cassette (ABC) transporters. Constitutive and antigen-stimulated S1P release was inhibited by MK571, an inhibitor of ABCC1 (MRP1), but not by inhibitors of ABCb1 (MDR-1, P-glycoprotein). Moreover, down-regulation of ABCC1 with small interfering RNA, which decreased its cell surface expression, markedly reduced S1P export from both rat RBL-2H3 and human LAD2 mast cells. Transport of S1P byABCC1 influenced migration of mast cells toward antigen but not degranulation. These findings have important implications for S1P functions in mast cell-mediated immune responses.