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NDP-MSH inhibits neutrophil migration through nicotinic and adrenergic receptors in experimental peritonitis

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Abstract

Melanocortin is a potent anti-inflammatory molecule. However, little is known about the effect of melanocortin on acute inflammatory processes such as neutrophil migration. In the present study, we investigated the ability of [Nle4, D-Phe7]-melanocyte-stimulating hormone (NDP-MSH), a semisynthetic melanocortin compound, in the inhibition of neutrophil migration in carrageenin-induced peritonitis model. Herein, subcutaneous pretreatment with NDP-MSH decreased neutrophil trafficking in the peritoneal cavity in a dose-dependent manner. NDP-MSH inhibited vascular leakage, leukocyte rolling, and adhesion and reduced peritoneal macrophage inflammatory protein 2, but not TNF-alpha, IL-1beta, IL-10, and keratinocyte-derived chemokine production. In addition, the effect on neutrophil migration was reverted by the pretreatment with both propranolol (a nonselective beta-adrenergic antagonist) and mecamylamine (a nonselective nicotinic antagonist) but not by splenectomy surgery. Moreover, NDP-MSH intracerebroventricular administration inhibited neutrophil migration, indicating participation of the central nervous system. Our results propose that the NDP-MSH effect may be due to a spleen-independent neuro-immune pathway that efficiently regulates excessive neutrophil recruitment to tissues.

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Acknowledgments

This work was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (grant numbers 150718/2010-1 and 478504/2010-1) and the Fundação de Amparo a Pesquisa do Estado de São Paulo (grant numbers 2011/11931-0, 2011/20343-4, and 2012/04237-2). We thank Ieda R. Santos, Sérgio R. Rosa, and Giuliana Bertozi for technical assistance and Dr. Carlos Henrique Cardoso Serezani for his critical reading of the manuscript.

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The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Av. Bandeirantes 3900, 14049-900, Ribeirão Preto, São Paulo, Brazil

    Jozi Figueiredo, Ana Elisa Ferreira, Rangel Leal Silva, Thiago Mattar Cunha, Sérgio Henrique Ferreira, Fernando de Queiróz Cunha & Alexandre Kanashiro

  2. Laboratory of Anti-Inflammatory Signaling and Surgical Immunology, Department of Surgery, UMDNJ–New Jersey Medical School, 185 South Orange Avenue, 07103 , Newark, NJ, USA

    Luis Ulloa

  3. Department of Pharmaceutical and Toxicological Chemistry, University of Naples “Federico II”, 80131, Naples, Italy

    Paolo Grieco

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  1. Jozi Figueiredo
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Correspondence to Alexandre Kanashiro.

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Figueiredo, J., Ferreira, A.E., Silva, R.L. et al. NDP-MSH inhibits neutrophil migration through nicotinic and adrenergic receptors in experimental peritonitis. Naunyn-Schmiedeberg's Arch Pharmacol 386, 311–318 (2013). https://doi.org/10.1007/s00210-013-0834-7

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  • DOI: https://doi.org/10.1007/s00210-013-0834-7

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