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

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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.