Activation of mitogen-activated protein kinase regulates eotaxin-induced eosinophil migration

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 al lergic inflammation observed in asthma, Here, we demonstrate that treatment of eosinophils with eotaxin induces the phosphorylation of the mitogen-act ivated protein kinases (MAPKs) p42 and p44, leading to kinase activation. B lockade of MAPK activation by the MAPK kinase inhibitor PD98059 leads to a dramatic decrease in eotaxin-induced eosinophil rolling in vivo and chemota xis in vitro. This blockade in the leukocyte migration process is consisten t with the observed inhibition of actin polymerization and rearrangement wi thin the eosinophil following treatment with MAPK inhibitor. It is suggeste d, therefore, that the intrinsic mechanism of eotaxin-induced eosinophil ro lling and migration involves activation of the p42/p44 MAPK, possibly throu gh regulation of the cytoskeletal rearrangements necessary for chemotaxis.