Activation of mitogen-activated protein kinase regulates eotaxin-induced eosinophil migration.
Activation of mitogen-activated protein kinase regulates eotaxin-induced eosinophil migration.
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DOI：
10.4049/jimmunol.163.3.1611
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发表时间：
1999-08
影响因子：
4.4
通讯作者：
S. Boehme;S. K. Sullivan;P. Crowe;Mark Santos;P. Conlon;P. Sriramarao;K. Bacon
中科院分区：
文献类型：
--
作者：
S. Boehme;S. K. Sullivan;P. Crowe;Mark Santos;P. Conlon;P. Sriramarao;K. Bacon
嗜酸性粒细胞趋化因子是一种有效的嗜酸性粒细胞化学引诱物，其在调节健康个体和与显著嗜酸性粒细胞浸润相关的疾病（例如在哮喘中观察到的过敏性炎症）中的嗜酸性粒细胞组织水平中起重要作用。在这里，我们证明了嗜酸性粒细胞与嗜酸细胞活化趋化因子的治疗诱导有丝分裂原活化蛋白激酶（MAPK）p42和p44的磷酸化，导致激酶激活。MAPK激酶抑制剂PD 98059阻断MAPK激活导致体内嗜酸性粒细胞趋化因子诱导的嗜酸性粒细胞滚动和体外趋化性显著降低。白细胞迁移过程中的这种阻断与用MAPK抑制剂处理后观察到的嗜酸性粒细胞内肌动蛋白聚合和重排的抑制一致。因此，它建议，嗜酸性粒细胞活化趋化因子诱导的嗜酸性粒细胞滚动和迁移的内在机制涉及p42/p44 MAPK的激活，可能通过调节细胞骨架重排所需的趋化性。
Eotaxin is a potent eosinophil chemoattractant that plays an important role in regulating eosinophil tissue levels both in healthy individuals and in diseases associated with significant eosinophil infiltrates, such as the allergic inflammation observed in asthma. Here, we demonstrate that treatment of eosinophils with eotaxin induces the phosphorylation of the mitogen-activated protein kinases (MAPKs) p42 and p44, leading to kinase activation. Blockade of MAPK activation by the MAPK kinase inhibitor PD98059 leads to a dramatic decrease in eotaxin-induced eosinophil rolling in vivo and chemotaxis in vitro. This blockade in the leukocyte migration process is consistent with the observed inhibition of actin polymerization and rearrangement within the eosinophil following treatment with MAPK inhibitor. It is suggested, therefore, that the intrinsic mechanism of eotaxin-induced eosinophil rolling and migration involves activation of the p42/p44 MAPK, possibly through regulation of the cytoskeletal rearrangements necessary for chemotaxis.