Abstract
Based on quantitative observations of platelets and leukocytes adhering to or aggregating on vascular endothelial cells activated by active oxygen generated from photochemical reactions, we quantitatively assessed interactions between endothelial and blood cells in the antecedent process to thrombus formation, and also evaluated the inhibitory effects of ibudilast (a phosphodiesterase inhibitor) on the adhesion and aggregation. Ibudilast inhibited the photochemically-induced adhesion between endothelial cells and platelets at concentrations of 10 μM or higher in a concentration-dependent manner, whereas aspirin did not inhibit the adhesion. Ibudilast also inhibited the adhesion of neutrophils to endothelial cells at concentrations of 1 μM or higher. Furthermore, we evaluated the inhibitory effects of ibudilast on morphological changes of endothelial cells and on subendothelial exposure, and the compound was shown to have inhibitory effects. These results suggest that ibudilast has composite antithrombotic activities, i.e., activities on endothelial cells in addition to previously reported antiplatelet activities. Future research should include the identification of interacting adhesion molecules and the assessment of endothelial cell-derived adhesion accelerators to elucidate the relationship between the substances and ibudilast activities.
