Role of the mitogen‐activated protein kinases and tyrosine kinases during leukotriene B4‐induced eosinophil activation

Role of the mitogen‐activated protein kinases and tyrosine kinases during leukotriene B4‐induced eosinophil activation
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丝裂原激活蛋白激酶和酪氨酸激酶在白三烯 B4 诱导的嗜酸性粒细胞激活过程中的作用

DOI:
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发表时间:
1998
影响因子:
5.5
通讯作者:
M. Giembycz
M. Giembycz
中科院分区:
医学3区
文献类型:
--
作者:
M. Lindsay;E. Haddad;J. Rousell;M. Teixeira;P. Hellewell;P. Barnes;M. Giembycz

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将豚鼠嗜酸性粒细胞暴露于白三烯B4 (LTB4; 1 μM)中导致H2O2的快速生成(NADPH氧化酶激活指数),刺激[3H]花生四烯酸(AA)的释放(磷脂酶A2活性指数),并促进CD18依赖的同型聚集。在类似的条件下,LTB4 (1 μM)诱导细胞外调节激酶- 1和2 (ERK‐1/2)的快速激活,但不诱导c‐jun N末端激酶46和54 (JNK‐46/54)或p38分裂原活化蛋白激酶(p38 MAP激酶)的快速激活。为了研究ERK‐1/2在嗜酸性粒细胞激活机制中的作用,我们使用了MAP激酶激酶‐1/2 (MEK‐1/2)的选择性抑制剂PD098059。然而,PD 098059在降低ERK‐1/2激活的浓度下对嗜酸性粒细胞的激活没有显著影响。相反,酪氨酸激酶抑制剂herbimycin a和lavendustin 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,这些实验的结果表明,控制嗜酸性粒细胞反应的途径不同,因为这些抑制剂在减少H2O2的产生方面比[3H]AA释放更有效,对同型聚集的影响很小。j . Leukoc。生物学报。64:555-562;1998.
Exposure of guinea‐pig eosinophils to leukotriene B4 (LTB4; 1 μM) 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 μM) 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. J. Leukoc. Biol. 64: 555–562; 1998.
DOI: --
发表时间: 1994-09
期刊: The Journal of biological chemistry
影响因子: --
作者:
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佛波酯或 fMLP 肽刺激后,人中性粒细胞中 MAP 激酶激活的蛋白激酶 2 被激活。
DOI: --
发表时间: 1996
期刊: Blood
影响因子: 20.3
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发表时间: 1997-03-01
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发表时间: 1996-03
期刊: The Journal of biological chemistry
影响因子: --
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