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

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- 1/4 ) 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- 1/4 in the mechanism of eosinophil activation, a selective inhibitor of MAP kinase kinase- 1/4 (MEK- 1/4 ), PD098059, was employed. However, PD 098059 at concentrations that attenuated ERK- 1/4 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.