The blood-endothelial cell interface is a region of significant importance in many physiologic and pathologic processes. Blood-borne macromolecules and cells gain access to the subendothelial space and extravascular tissues by traversing the endothelium. Yet the various factors responsible for modulation of this process remain only partially elucidated. Several agents were found to be involved in this process, including nitric oxide (NO) and vascular endothelial growth factor (VEGF). It is known that under stress conditions (e.g., inflammation), NO can modulate the permeability of endothelial-cell monolayers to low-density mononuclear cells (LDMNCs). However, it is not known if NO can modulate such effects in the absence of inflammatory stimulation. In the present study, we utilized a Transwell chamber model to examine endothelial-cell monolayer permeability to LDMNCs in the absence of inflammatory stimuli. We noted that NO donor and L-arginine increased transendothelial-cell migration, whereas nitric oxide synthase (NOS) inhibition decreased migration. These effects were not significantly abrogated by VEGF antibody, suggesting that they were not VEGF-dependent.
