Sphingosine 1-phosphate induces extracellular matrix invasion and seprase activity in human endothelial cells.

1151 Sphingosine 1-phosphate (Sph-1-P), a bioactive lysophospholipid present in the plasma, is released from activated platelets. Our previous study demonstrated that Sph-1-P promoted the spreading on and migration of human umbilical vein endothelial cells (HUVEC) through the extracellular matrix (ECM), suggesting a possible induction of cell surface proteases in the Sph-1-P activated endothelial cells. Here we provide the evidence that seprase, a type II transmembrane serine protease (TTSP) usually absent in tissue cells, can be induced in endothelial cells activated by Sph-1-P. We show by immunoblot analysis using anti-seprase monoclonal antibodies (mAbs) that Sph-1-P enhanced expression of seprase in a time- and dose-dependent manner in HUVEC. The Sph-1-P inducible seprase could be blocked by pertussis toxin and by C3 transferase, which inactivate Gi-type heterotrimetric G proteins and Rho, respectively. These results show that Sph-1-P can regulate migration of endothelial cells by inducing seprase expression, which, in turn, is mediated through a Gi-coupled cell surface receptor and the Rho protein.