Lindsay M A, Haddad E B, Rousell J, Teixeira M M, Hellewell P G, Barnes P J, Giembycz M A
Thoracic Medicine, Imperial College School of Medicine at the National Heart and Lung Institute, London, United Kingdom.
J Leukoc Biol. 1998 Oct;64(4):555-62. doi: 10.1002/jlb.64.4.555.
Exposure of guinea-pig eosinophils to leukotriene B4 (LTB4; 1 microM) resulted in a rapid generation of H2O2 (index of NADPH oxidase activation), stimulated [3H]arachidonic acid (AA) release (index of phospholipase A2 activity), and promoted CD18-dependent homotypic aggregation. Under similar conditions, LTB4 (1 microM) induced a rapid activation of extracellular-regulated kinases-1 and 2 (ERK-1/2) but not c-jun N-terminal kinases 46 and 54 (JNK-46/54) or p38 mitogen-activated protein kinase (p38 MAP kinase). To examine the role of ERK-1/2 in the mechanism of eosinophil activation, a selective inhibitor of MAP kinase kinase-1/2 (MEK-1/2), PD098059, was employed. However, PD 098059 at concentrations that attenuated ERK-1/2 activation had no significant affect on eosinophil activation. In contrast, a role for tyrosine kinases in LTB4-induced eosinophil activation was suggested by studies with the tyrosine kinase inhibitors, herbimycin A and lavendustin A. However, the results of those experiments implied divergent pathways for the control of eosinophil responses because the inhibitors were more effective at attenuating H2O2 generation than [3H]AA release, and had little effect on homotypic aggregation.
将豚鼠嗜酸性粒细胞暴露于白三烯B4（LTB4；1微摩尔）会导致过氧化氢迅速生成（NADPH氧化酶激活指标）、刺激[3H]花生四烯酸（AA）释放（磷脂酶A2活性指标）并促进CD18依赖性同型聚集。在类似条件下，LTB4（1微摩尔）可迅速激活细胞外调节激酶-1和2（ERK-1/2），但不会激活c-jun氨基末端激酶46和54（JNK-46/54）或p38丝裂原活化蛋白激酶（p38 MAP激酶）。为了研究ERK-1/2在嗜酸性粒细胞激活机制中的作用，使用了丝裂原活化蛋白激酶激酶-1/2（MEK-1/2）的选择性抑制剂PD098059。然而，能减弱ERK-1/2激活的浓度下的PD 098059对嗜酸性粒细胞激活没有显著影响。相比之下，酪氨酸激酶抑制剂赫曲霉素A和拉文达ustin A的研究表明酪氨酸激酶在LTB4诱导的嗜酸性粒细胞激活中起作用。然而，那些实验的结果暗示了控制嗜酸性粒细胞反应的不同途径，因为这些抑制剂在减弱过氧化氢生成方面比[3H]AA释放更有效，并且对同型聚集影响很小。
