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Pathways for eosinophil lipid body induction: differing signal transduction in cells from normal and hypereosinophilic subjects
Author(s) -
Bozza Patricia T.,
Yu Wengui,
Cassara Jessica,
Weller Peter F.
Publication year - 1998
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 - 10.1002/jlb.64.4.563
Subject(s) - biology , eosinophil , signal transduction , hypereosinophilic syndrome , immunology , microbiology and biotechnology , transduction (biophysics) , eosinophilia , biochemistry , asthma
Although lipid bodies, inducible cytoplasmic inclusions active in arachidonic acid metabolism, are abundant in activated leukocytes, including eosinophils, mechanisms for eosinophil lipid body formation are not certain. Eosinophils from hypereosinophilic syndrome (HES) donors contained about twice (~18/cell) as many lipid bodies as eosinophils from normal donors (~10/cell). By immunocytochemistry both 5‐ and 15‐lipoxygenases were localized at lipid bodies in HES eosinophils. Platelet‐activating factor (PAF) induced rapid, receptor‐mediated increases in lipid bodies in normal and HES eosinophils. Protein kinase C (PKC) inhibitors, chelerythrine and calphostin C, inhibited PAF‐induced lipid body formation partially in normal and HES eosinophils. In HES, but not normal, eosinophils, PAF‐induced lipid body formation was completely blocked by two tyrosine kinase inhibitors, herbimycin A and genistein, which were not acting on 5‐lipoxygenase because they also blocked 5‐HETE‐induced lipid body formation in HES, and not normal, eosinophils. After 24 h culture with eosinophil growth factor cytokines [interleukin (IL)‐3, IL‐5, and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) or GM‐CSF alone but not IL‐5 or IL‐3 alone], normal eosinophils were induced to exhibit an HES‐like phenotype, including increased lipid body numbers and tyrosine kinase‐dependent signaling for PAF‐induced lipid body formation. Thus, signal transduction mechanisms involved in PAF‐induced lipid body formation in eosinophils can be differentially recruited. Tyrosine kinase‐dependent signaling is not involved in normal eosinophils, but is active in HES eosinophils and in normal eosinophils cultured with GM‐CSF. PKC‐ and tyrosine kinase‐dependent pathways are involved in the formation of eosinophil lipid bodies, which may facilitate enhanced synthesis of lipoxygenase‐derived eicosanoids. J. Leukoc. Biol . 64: 563–569; 1998.