| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1935412 | Biochemical and Biophysical Research Communications | 2008 | 6 Pages |
The phosphorylated derivative of the immunosuppressant FTY720 interacts with and modulates the function of sphingosine-1-phosphate (S1P)-receptors. We observed a significant reduction of endothelial surface binding of a S1P1-specific antibody after FTY720 treatment of 6 h and longer, which was associated with a reduced healing after mechanic injury, impaired angiogenesis and enhanced adhesion molecule expression. FTY720 (5 h) had no impact on the expression of S1P1- or S1P3-encoding transcripts. Notably, pre-treatment of cells with FTY720 for only 30 min, which did not reduce S1P1 surface expression, inhibited the rapid S1P- and SEW2871- (a S1P1 agonist) induced cortical actin formation and cell migration. FTY720 was effective at concentrations as low as 5 nM.FTY720 at therapeutic concentrations may be harmful by impairing important endothelial functions. Interestingly, FTY720 inhibited endothelial actin remodelling and cell migration without decreasing S1P1 surface expression.
