Journal of Leukocyte Biology
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Originally published online as doi:10.1189/jlb.0906548 on February 8, 2007

Published online before print February 8, 2007
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(Journal of Leukocyte Biology. 2007;81:1245-1251.)
© 2007 by Society for Leukocyte Biology

Modulation of eosinophil activation in vitro by a nicotinic receptor agonist

Marie-Renée Blanchet, Anick Langlois, Evelyne Israël-Assayag, Marie-Josée Beaulieu, Claudine Ferland, Michel Laviolette and Yvon Cormier1

Centre de Recherche, Hôpital Laval, Institut Universitaire de Cardiologie et de Pneumologie de l’Université Laval, Ste-Foy, Québec, Canada

1 Correspondence: Centre de Pneumologie, Hôpital Laval, 2725 Chemin Ste-Foy, Ste-Foy, Québec, Canada, G1V 4G5. E-mail: yvon.cormier{at}med.ulaval.ca

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 {alpha}-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 {alpha}-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.

Key Words: chemotaxis • dimethylphenylpiperazinium • leukotriene • intracellular calcium




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