TY - JOUR
T1 - Role of the mitogen-activated protein kinases and tyrosine kinases during leukotriene B4-induced eosinophil activation
AU - Lindsay, Mark A.
AU - Haddad, El Bdaoui
AU - Rousell, Jonathan
AU - Teixeira, Mauro M.
AU - Hellewell, Paul G.
AU - Barnes, Peter J.
AU - Giembycz, Mark A.
PY - 1998/10/1
Y1 - 1998/10/1
N2 - 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.
AB - 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.
KW - Homotypic aggregation
KW - NADPH oxidase
KW - Phospholipase A
UR - http://www.scopus.com/inward/record.url?scp=0031687981&partnerID=8YFLogxK
U2 - 10.1002/jlb.64.4.555
DO - 10.1002/jlb.64.4.555
M3 - Article
C2 - 9766637
AN - SCOPUS:0031687981
SN - 0741-5400
VL - 64
SP - 555
EP - 562
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 4
ER -