Role of vascular cell adhesion molecule-1 and platelet-activating factor in selective eosinophil migration across...

To determine the role of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in mediating selective eosinophil migration across vascular endothelial cells, we examined the effect of anti-ICAM-1 monoclonal antibody (mAb) and anti-VCAM-1 mAb on transendothelial migration of human eosinophils and neutrophils across IL-1- and IL-1-stimulated cultured vascular endothelial cells. We also studied the effect of a selective antagonist for platelet-activating factor (PAF) on the transendothelial migration of eosinophils and neutrophils. Transendothelial migration of eosinophils was increased by stimulation of the endothelial cells with IL-1 and IL-4, the latter of which has been shown to selectively induce VCAM-1 expression on the endothelial cells. On the other hand, neutrophil transendothelial migration was increased only by IL-1. Eosinophil migration across IL-4-stimulated endothelial cells was decreased by anti-ICAM-1 mAb and anti-VCAM-1 mAb. A selective PAF antagonist E6123 also decreased eosinophil migration across IL-4-stimulated endothelial cells. Eosinophil migration across IL-1-stimulated endothelial cells was also decreased by anti-ICAM-1 mAb and anti-VCAM-1 mAb in the presence of PAF antagonist. In contrast, neutrophil migration across IL-1-stimulated endothelial cells was decreased by anti-ICAM-1 mAb but not anti-VCAM-1 mAb. PAF antagonist alone or together with anti-VCAM-1 had no significant effect on IL-1-induced neutrophil transendothelial migration. These results indicate that VCAM-1 and PAF play an important role in mediating selective eosinophil migration across vascular endothelial cells.