Komatsu H, Nagasawa M, Okumoto T
Research Laboratories, Yoshitomi Pharmaceutical Industries Ltd, Saitama, Japan.
Int J Immunopharmacol. 1993 Aug;15(6):737-44. doi: 10.1016/0192-0561(93)90146-p.
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.
研究了血小板活化因子（PAF）拮抗剂Y-24180（4-(2-氯苯基)-2-[2-(4-异丁基苯基)乙基]-6,9-二甲基-6H-噻吩并[3,2-f][1,2,4]三唑并[4,3-a][1,4]二氮杂卓）对人脐静脉内皮细胞白细胞黏附的影响。Y-24180以浓度依赖性方式抑制白三烯B4激活的豚鼠腹腔渗出细胞与内皮细胞的黏附。另一种PAF拮抗剂WEB2086未显示出抑制作用。Y-24180的抑制作用不受PAF添加的影响。Y-24180对白细胞介素-1β激活的内皮细胞上细胞间黏附分子-1或内皮细胞-白细胞黏附分子-1的表达没有影响，而它抑制了白三烯B4激活的人外周血多形核细胞上CD18抗原的表达，抑制了它们与白细胞介素-1β激活的内皮细胞的黏附。在恶唑酮诱导的小鼠耳部水肿中，这涉及炎症细胞浸润的迟发型超敏反应，Y-24180剂量依赖性地抑制耳部重量的增加，但WEB2086没有。这些结果表明，Y-24180不仅抑制PAF的作用，还通过抑制CD18抗原的表达来抑制白细胞的黏附，从而抑制炎症细胞的浸润。
