Patrick R A, Peters P A, Issekutz A C
CIBA-GEIGY Corporation, Pharmaceuticals Division, Department of IOE/Research, Summit, NJ 07901.
Agents Actions. 1993 Nov;40(3-4):186-90. doi: 10.1007/BF01984060.
Ebselen is a seleno-organic anti-inflammatory compound with glutathione peroxidase-like activity that has the unique characteristic of mediating the isomerization of 5-HETE and LTB4 to their biologically inactive trans isomers, both directly in fluid phase and indirectly through metabolic pathways in stimulated peripheral blood leukocytes. LTB4 is an inflammatory mediator with potent chemotactic activity for neutrophilic leukocytes. We studied the effects of ebselen on the chemotactic and chemokinetic responses with human-blood-derived neutrophils. With the use of 120-microns-thick 5-microns-pore durapore filters and low BSA concentrations (0.05%) in the chemotaxis buffers, ebselen was evaluated for its effect on both chemotactic and chemokinetic responses to LTB4, C5a, and fMLP. Ebselen at 3-20 microM concentrations inhibited both chemotactic and chemokinetic responses to optimal concentrations of LTB4 without altering chemotactic responses to C5a or fMLP. Likewise, ebselen at 20 microM specifically inhibited LTB4-stimulated transendothelial migration of neutrophils, while not altering responses to C5a nor fMLP.
依布硒啉是一种具有谷胱甘肽过氧化物酶样活性的有机硒抗炎化合物，其独特之处在于能在液相中直接以及通过刺激外周血白细胞中的代谢途径间接介导5-羟二十碳四烯酸（5-HETE）和白三烯B4（LTB4）异构化为其生物活性较低的反式异构体。LTB4是一种对嗜中性白细胞具有强大趋化活性的炎症介质。我们研究了依布硒啉对人血来源的嗜中性粒细胞趋化和化学动力学反应的影响。在趋化缓冲液中使用120微米厚、5微米孔径的聚偏氟乙烯（Durapore）滤膜和低牛血清白蛋白（BSA）浓度（0.05%），评估依布硒啉对LTB4、C5a和N-甲酰甲硫氨酸-亮氨酸-苯丙氨酸（fMLP）趋化和化学动力学反应的影响。3至20微摩尔浓度的依布硒啉抑制了对最佳浓度LTB4的趋化和化学动力学反应，而不改变对C5a或fMLP的趋化反应。同样，20微摩尔的依布硒啉特异性抑制LTB4刺激的嗜中性粒细胞跨内皮迁移，同时不改变对C5a和fMLP的反应。
