BIO-1211对嗜酸粒细胞趋化和聚集及释放介质的影响

Effects of BIO-1211 on eosinophil chemotaxis,recruitment and mediator release

目的 :研究 VL A- 4拮抗剂 BIO- 12 11对嗜酸粒细胞趋化、聚集和释放的影响。方法 :采用离体方法测定血小板活化因子 (PAF)诱导的嗜酸性粒细胞反应 ,整体方法观察嗜酸性粒细胞聚集和释放反应。结果 :BIO- 12 11能明显抑制 PAF对嗜酸性粒细胞的趋化作用 ,BIO- 12 114× 10 -11、4× 10 -10、4× 10 -9mol· L-1的抑制率分别为2 4 .9%、2 9.9%、31.3%。BIO- 12 111、3、10 mg·kg-1单次腹腔给药 ,呈剂量依赖性抑制大鼠葡聚糖凝胶引起的腹腔嗜酸粒细胞聚集 ,抑制率分别为 6 0 .3%、6 8.9%和 72 .9% (P<0 .0 5 ) ,但不能抑制嗜酸性粒细胞释放嗜酸细胞过氧化物酶。结论 :BIO- 12 11抑制嗜酸性粒细胞趋化和聚集 ,减轻局部炎症反应 ,有可能发展成为一种新的抗变态反应性药物。

Objective: To study the effects of very late antigen(VLA) antagonist BIO-1211 on eosinophil chemotaxis,recruitment and mediator release. Methods:Eosinophil chemotaxis was induced by platelet activating factor(PAF) in vitro and eosinophil recruitment and release were determined in vivo. Results:VLA antagonist BIO-1211 inhibited eosinophil chemotaxis induced by PAF. The inhibitory rates at 4×10 -11,4×10 -10,4×10 -9 mol·L -1 were 24.9%,29.9%,and 31.3%,respectively. Pretreatment by BIO-1211 1,3 and 10 mg·kg -1 intraperitoneally inhibited the recruitment of eosinophils in PAF in the rat induced by Sephadex in a dose-dependent manner. Inhibitory rates were 60.3%,68.9%,and 72.9%(P<0.05),respectively.BIO-1211 did not inhibit eosinophil peroxi-dase(EPO) release from eosinophils.Conclusion:BIO-1211 inhibits eosinophil chemotaxis and recruitment,allevia-tes local inflammation,and may represent a new type of drug for allergic diseases.