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Differential modulation of mediator release from human basophils and mast cells by mizolastine
Author(s) -
Triggiani M.,
Giannattasio G.,
Balestrieri B.,
Granata F.,
Gelb M. H.,
De Paulis A.,
Marone G.
Publication year - 2004
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/j.1365-2222.2004.01851.x
Subject(s) - mediator , immunology , mast cell , mast (botany) , differential (mechanical device) , microbiology and biotechnology , chemistry , biology , physics , thermodynamics
Summary Background Basophils and mast cells play a major role in the pathogenesis of allergic disorders by releasing several proinflammatory mediators. Some histamine H 1 receptor antagonists exert anti‐inflammatory activities by modulating mediator release from basophils and mast cells. Objective To study the in vitro effects of mizolastine, an H 1 receptor antagonist, on the release of eicosanoids, histamine and IL‐4 from human basophils and lung mast cells. Methods and results Mizolastine (10 −7 –10 −5 m ) concentration‐dependently inhibited the release of cysteinyl leukotriene C 4 from anti‐IgE‐stimulated basophils (IC 50 : 3.85±0.28 μ m ) and mast cells (IC 50 : 3.92±0.41 μ m ). The same concentrations of mizolastine did not affect anti‐IgE‐induced prostaglandin D 2 release from lung mast cells. In contrast, mizolastine enhanced up to 80% IgE‐mediated histamine release (EC 50 : 4.63±0.14 μ m ) from basophils, but not from mast cells and it significantly potentiated IL‐4 release from basophils induced by anti‐IgE. Mizolastine did not affect histamine release from basophils induced by formyl peptide, whereas it inhibited cysteinyl leukotriene C 4 release (IC 50 : 1.86±0.24 μ m ). Blockade of cytosolic phospholipase A 2 and arachidonic acid mobilization by pyrrolidine‐1 did not alter the effect of mizolastine on histamine release from basophils, thereby excluding accumulation of arachidonic acid metabolic intermediates as the cause of this effect. Mizolastine did not influence anti‐IgE‐induced activation of extracellular signal‐regulated kinase‐1 and ‐2 (ERK‐1 and ‐2) in human basophils. Conclusions Mizolastine efficiently inhibits LTC 4 synthesis in human basophils and mast cells presumably by interfering with 5‐lipoxygenase. In contrast, it enhances histamine and IL‐4 release only from anti‐IgE‐stimulated basophils. Therefore, mizolastine differentially regulates the production of mediators from basophils and mast cells in a cell‐ and stimulus‐specific fashion.