Role of the mitogen‐activated protein kinases and tyrosine kinases during leukotriene B 4 ‐induced eosinophil activation

Exposure of guinea‐pig eosinophils to leukotriene B 4 (LTB 4 ; 1 μM) resulted in a rapid generation of H 2 O 2 (index of NADPH oxidase activation), stimulated [ 3 H]arachidonic acid (AA) release (index of phospholipase A 2 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 LTB 4 ‐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 H 2 O 2 generation than [ 3 H]AA release, and had little effect on homotypic aggregation. J. Leukoc. Biol . 64: 555–562; 1998.