Modulation of eosinophil activation in vitro by a nicotinic receptor agonist

Nicotinic receptor agonists decreased the infiltration of eosinophils into the lung and airways in a mouse model of asthma. To better understand the mechanisms implicated in this anti‐inflammatory phenomenon, the expression of nicotinic acetylcholine receptors (nAChRs) and the effect of dimethylphenylpiperazinium (DMPP), a nonselective nAChR agonist, on human blood eosinophils were studied. The expression of α‐3, ‐4, and ‐7 nAChR subunits on human blood eosinophils was measured by cell ELISA and immunocytochemistry. mRNA expression for all three subunits was evaluated by quantitative RT‐PCR. The effect of DMPP on leukotriene C4 (LTC4) and matrix metalloproteinase‐9 (MMP‐9) production, eosinophil migration, and intracellular calcium mobilization was measured. The results show that the α‐3, ‐4, and ‐7 nAChR subunits and mRNAs are expressed by blood eosinophils. In vitro treatment of these cells with various concentrations of DMPP reduced platelet‐activating factor (PAF)‐induced LTC4 production significantly. DMPP (160 μM) decreased eotaxin, and 5‐oxo‐6,8,11,14‐eicosatetranoic acid induced eosinophil migration through Matrigel by 40.9% and 55.5%, respectively. This effect was reversed by the nAChR antagonist mecamylamine. In addition, DMPP reduced MMP‐9 release and the inositol 1,4,5‐triphosphate‐dependent intracellular calcium increase provoked by PAF. Taken together, these results indicate that functional nAChRs are expressed on eosinophils and that nAChR agonists down‐regulate eosinophil function in vitro. These anti‐inflammatory effects could be of interest in the treatment of allergic asthma.