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.
Komatsu
H
H
Research Laboratories, Yoshitomi Pharmaceutical Industries Ltd, Saitama, Japan.
Nagasawa
M
M
Okumoto
T
T
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D001381:Azepines / Q000494:pharmacology*; D018821:CD18 Antigens; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000032:analysis; D002478:Cells, Cultured; D019040:E-Selectin; D004487:Edema / Q000517:prevention & control; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D006168:Guinea Pigs; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007962:Leukocytes / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D014230:Triazoles / Q000494:pharmacology*; D014471:Umbilical Veins
D015703:Antigens, CD; D001381:Azepines; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D010972:Platelet Activating Factor; D014230:Triazoles; C052518:WEB 2086; C068035:4-(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; D018799:Intercellular Adhesion Molecule-1