Roles of sphingosine-1-phosphate foreosinophil localization and function in mice

我们监测了FTY720给药后IL-5转基因小鼠嗜酸粒细胞数量的变化。FTY720处理的IL-5转基因小鼠外周血中嗜酸性粒细胞数量显著减少，提示嗜酸性粒细胞对S1P-S1P1敏感。相应地，嗜酸性粒细胞通过Transwell试验显示对S1P的趋化反应。此外，当S1P介导的信号转导被FTY720处理中断时，嗜酸性粒细胞在骨髓中聚集。然后，我们利用反复应用半抗原诱导的小鼠特应性皮炎模型，显示了皮肤嗜酸性粒细胞的增加。在最后一次激发前给予FTY720可减少皮肤嗜酸性粒细胞的数量，同时降低耳肿胀反应和晚期反应。这些发现表明，S1P-S1P1信号调节嗜酸性粒细胞从骨髓中流出，并影响皮肤嗜酸性粒细胞的定位和由此产生的晚期反应。

We monitored numerical alternations of eosinophils in IL-5 transgenic mice following FTY720 administration. The number of circulating eosinophils was significantly decreased in IL-5 transgenic mice treated by FTY720,suggesting that eosinophils are S1P-S1P1 sensitive. Accordingly, eosinophils showed a chemotactic response to S1P through a transwell assay. Additionally,eosinophils accumulated in the bone marrow, when S1P mediated signaling was disrupted by FTY720 treatment. We then showed the increment of cutaneous eosinophils using a murine atopic dermatitis model induced by repeated hapten application. FTY720 administration before the final challenge decreased the number of cutaneous eosinophils along with reduction of the ear swelling response, of the late phase reaction. These findings suggest that S1P-S1P1 signaling regulates the egress of eosinophils from the bone marrow and affects cutaneous eosinophil localization and resultant late phase reaction.