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Pharmacological Beta-Adrenergic Receptor Activation Attenuates Neutrophil Recruitment by a Mechanism Dependent on Nicotinic Receptor and the Spleen

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Abstract

The aim of this study was to identify the effect of beta-adrenergic receptor activation on neutrophil migration in experimental peritonitis elucidating the neuroimmune components involved such as nicotinic receptors and the spleen. Mice pre-treated with mecamylamine (nicotinic antagonist) and propranolol (beta-adrenergic antagonist) or splenectomized animals were treated with isoproterenol (beta-adrenergic agonist) prior to intraperitoneal injection of carrageenan. After 4 h, the infiltrating neutrophils and the local cytokine/chemokine levels were evaluated in the peritoneal lavage. The effect of isoproterenol on neutrophil chemotaxis was investigated in a Boyden chamber. Isoproterenol inhibited neutrophil trafficking, reducing the cytokine/chemokine release and neutrophil chemotaxis. Surprisingly, the isoproterenol effect on neutrophil migration was totally reverted by splenectomy and mecamylamine pre-treatment. In contrast, the inhibitory effect of nicotine on neutrophil migration was abrogated only by splenectomy but not by propranolol pre-treatment. Collectively, our data show that beta-adrenergic receptor activation regulates the acute neutrophil recruitment via splenic nicotinic receptor.

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Acknowledgments

The research leading to these results has received funding from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, grants 11/20343-4, 11/19670-0, 12/04237-2, 13/01466-3, and 13/08216-2), National Council for Scientific and Technological Development (CNPq, grant 142068/2012-8), and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, grant 451/2008). The authors thank Matheus C. Mangetti, Ieda R. Santos, Sérgio R. Rosa, and Giuliana Bertozi for the technical assistance.

Author Contributions

R.L.S., F.Q.C., and A.K. designed the study. R.L.S., J.G.F., and A.K. performed the mouse experiments. F.V.C. performed the chemotaxis assay. R.L.S. and A.K. wrote the manuscript. G.S.B., S.H.F. and T.M.C. reviewed the manuscript.

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Correspondence to Rangel L. Silva or Alexandre Kanashiro.

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All experiments were conducted in accordance with the National Institutes of Health guidelines on the welfare of experimental animals and with the approval of the Ethics Committee of the Faculty of Medicine of Ribeirão Preto (University of São Paulo).

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Silva, R.L., Castanheira, F.V., Figueiredo, J.G. et al. Pharmacological Beta-Adrenergic Receptor Activation Attenuates Neutrophil Recruitment by a Mechanism Dependent on Nicotinic Receptor and the Spleen. Inflammation 39, 1405–1413 (2016). https://doi.org/10.1007/s10753-016-0372-9

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