The leukotriene C4 transporter MRP1 regulates CCL19 (MIP-3β, ELC)-dependent mobilization of dendritic cells to lymph nodes
The leukotriene C4 transporter MRP1 regulates CCL19 (MIP-3β, ELC)-dependent mobilization of dendritic cells to lymph nodes
复制标题
DOI：
10.1016/s0092-8674(00)00179-3
复制
发表时间：
2000-11-22
期刊：
影响因子：
64.5
通讯作者：
Randolph, GJ
中科院分区：
文献类型：
--
作者：
Robbiani, DF;Finch, RA;Randolph, GJ
携带抗原的树突状细胞(DC)从外周组织进入淋巴结后，适应性免疫反应开始。在这里，我们证明了DC从皮肤到淋巴结的迁移利用了白三烯C-4(LTC4)转运体多药耐药相关蛋白1(MRP1)。外源性半胱氨酰白三烯LTC4或LTD可使MRP1(-/-)小鼠外周血树突状细胞从表皮向淋巴管的迁移减少。在体外，这些半胱氨酸基白三烯促进了对趋化因子CCL19的最佳趋化，但对其他相关趋化因子没有促进作用。CCL19在体内的拮抗作用阻止了DC迁移出表皮。因此，MRP-1显然是通过转运LTC4来调节DC向淋巴结的迁移，而LTC4又促进了对CCL19的趋化作用和从表皮动员DC。
Adaptive immune responses begin after antigen-bearing dendritic cells (DCs) traffic from peripheral tissues to lymph nodes. Here, we show that DC migration from skin to lymph nodes utilizes the leukotriene C-4 (LTC4) transporter multidrug resistance-associated protein 1 (MRP1). DC mobilization from the epidermis and trafficking into lymphatic vessels was greatly reduced in MRP1(-/-) mice, but migration was restored by exogenous cysteinyl leukotrienes LTC4 or LTD,. In vitro, these cysteinyl leukotrienes promoted optimal chemotaxis to the chemokine CCL19, but not to other related chemokines. Antagonism of CCL19 in vivo prevented DC migration out of the epidermis. Thus, MRP-1 regulates DC migration to lymph nodes, apparently by transporting LTC4, which in turn promotes chemotaxis to CCL19 and mobilization of DCs from the epidermis.