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Regulation of mediator secretion in human basophils by p38 mitogen‐activated protein kinase: phosphorylation is sensitive to the effects of phosphatidylinositol 3‐kinase inhibitors and calcium mobilization
Author(s) -
Gibbs Bernhard F.,
Plath Katharina E. S.,
Wolff Helmut H.,
Grabbe Jürgen
Publication year - 2002
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.72.2.391
Subject(s) - wortmannin , mapk/erk pathway , microbiology and biotechnology , biology , phosphatidylinositol , kinase , p38 mitogen activated protein kinases , protein kinase a , basophil , immunology , immunoglobulin e , antibody
Although human basophils modulate allergic diseases by secreting histamine, leukotriene C 4 , interleukin (IL)‐4, and IL‐13, the intermediary signals controlling the release of these mediators are poorly understood. Here, we show that p38 mitogen‐activated protein kinase (MAPK) crucially affects basophil activation following stimulation with various secretagogues. Phosphorylation of p38 MAPK occurred within 5 min following anti‐immunoglobulin (Ig)E stimulation, but was more rapidly activated in basophils stimulated with formyl‐Met‐Leu‐Phe or A23187. Additionally, activation of p38 MAPK to the above stimuli was dependent on extracellular influx and intracellular mobilization of calcium. SB 203580, a specific p38 MAPK inhibitor, blocked anti‐IgE‐induced secretion of all basophil mediators and reduced not only p38 MAPK, but also extracellular signal‐regulated kinases 1 and 2 activity, whereas the MAPK antagonist, PD 098059, did not affect p38 MAPK. IgE‐dependent activation of p38 MAPK and MKK3/6 was affected by LY 294002 and wortmannin, suggesting that these kinases are targets for phosphatidylinositol 3 kinase (PI 3‐K). We conclude that p38 MAPK is a pivotal regulator of basophil function downstream of PI 3‐K activation and calcium mobilization.