The Puzzling Role of TRAIL in Endothelial Cell Biology

To the Editor:In their study published online in Arteriosclerosis, Thrombosis, and Vascular Biology , O’Brien et al demonstrate that activated protein C (APC) decreases tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) expression in endothelial cells.1 Although the molecular mechanism by which APC decreases the expression of TRAIL mRNA and protein via an Egr-1/Erk-1/2 pathway appears convincing, much less clear is whether the downregulation of TRAIL reflects a physiological relevant decrease of surface TRAIL or TRAIL release by endothelial cells. In fact, we have never detected surface TRAIL by flow cytometry in human umbilical vein endothelial cells (HUVECs), cultured with or without TNF-α (Figure). On the other hand, surface …