Synergistic induction of t-PA by vascular endothelial growth factor and basic fibroblast growth factor and localization of t-PA to Weibel-Palade bodies in bovine microvascular endothelial cells

Endothelial cell mi-ration is stimulated by members of the vascular endothe lial growth factor (VEGF) and basic fibroblast growth factor (bFGF) familie s, and is dependent on extracellular proteolytic activity provided by enzym es of the plasminogen activator (PA) system. Here we report that in bovine microvascular endothelial cells (BME cells), bFGF principally increased uro kinase-type PA (u-PA) while tissue-type PA (t-PA) was increased mainly by V EGF. In bovine aortic endothelial cells (BAE cells), bFGF increased u-PA, w hereas VEGF had no effect. Co-added bFGF and VEGF increased t-PA mRNA level s and enzyme activity in both cell types in a synergistic manner. Tissue-ty pe plasminogen activator (t-PA) immunoreactivity colocalized with von Wille brand factor, a marker for Weibel-Palade bodies. Co-added bFGF and VEGF inc reased the number of t-PA-positive cells as well as the number of t-PA-posi tive granules per cell. Localization of t-PA in regulated storage granules endows endothelial cells with the potential to rapidly increase proteolytic activity in the pericellular environment.