Action sites of antiallergic drugs on human neutrophils.

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Sites of the inhibitory action of antiallergic drugs (azelastine, oxatomide, tranilast, repirinast and amlexanox) on human neutrophils were investigated by measuring leukotriene B<SUB>4</SUB> formation, arachidonic acid release and superoxide generation. Results obtained in this study were as follows: (i) Formations of leukotriene B<SUB>4</SUB> by neutrophils activated with a calcium ionophore (A23187) were effectively inhibited by all types of antiallergic drugs examined here, although the required concentrations were within a range of 20-200 μM. (ii) Releases of arachidonic acid from activated cells were diminished by azelastine and oxatomide that were classified as basic antiallergic drugs. On the contrary, acidic antiallergic agents including repirinast, amlexanox and tranilast enhanced the arachidonic acid liberation. (iii) Generations of superoxide from neutrophils activated with either phorbol 12-myristate 13-acetate or n-formyl-methionyl-leucyl-phenylalanine were effectively diminished only by the basic antiallergic drugs.
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