Inhibition of leukocyte adhesion to endothelial cells of human umbilical vein by Y-24180, an antagonist of platelet-activating factor.

Effect of Y-24180 (4-(2-chlorophenyl)-2-[2-(4-isobutylphenyl)ethyl]-6,9-dimethyl-6H- thieno [3,2-f][1, 2, 4]triazolo[4,3-a][1,4]diazepine), an antagonist of platelet-activating factor (PAF), on adhesion of leukocytes to endothelial cells of human umbilical vein was examined. Y-24180 inhibited the adhesion of guinea-pig peritoneal exudate cells activated by leukotriene B4 to endothelial cells in a concentration-dependent manner. WEB2086, another PAF antagonist, did not show the inhibitory effect. Inhibition by Y-24180 was not influenced by addition of PAF. Y-24180 had no effect on the expression of intercellular adhesion molecule-1 or endothelial-leukocyte adhesion molecule-1 on endothelial cells activated with interleukin-1 beta, while it suppressed the expression of CD18 antigen on human peripheral blood polymorphonuclear cells activated with leukotrien B4, inhibiting their adhesion to endothelial cells activated with interleukin-1 beta. In oxazolone-induced ear edema in mice, which involves delayed-type hypersensitivity with infiltration by inflammatory cells, Y-24180 dose-dependently inhibited the increase in ear weights, but WEB2086 did not. These results indicate that Y-24180 inhibits not only the actions of PAF but also the adhesion of leukocytes by suppressing the expression of CD18 antigen, inducing the inhibition of infiltration by inflammatory cells.