TY - JOUR
T1 - NDP-MSH inhibits neutrophil migration through nicotinic and adrenergic receptors in experimental peritonitis
AU - Figueiredo, Jozi
AU - Ferreira, Ana Elisa
AU - Silva, Rangel Leal
AU - Ulloa, Luis
AU - Grieco, Paolo
AU - Cunha, Thiago Mattar
AU - Ferreira, Sérgio Henrique
AU - Cunha, Fernando De Queiróz
AU - Kanashiro, Alexandre
N1 - Funding Information:
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.
PY - 2013/4
Y1 - 2013/4
N2 - 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.
AB - 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.
KW - Adrenergic receptors
KW - Anti-inflammatory cholinergic pathway
KW - Melanocortin
KW - Neuroimmunomodulation
KW - Neutrophil migration
KW - Nicotinic receptors
UR - https://www.scopus.com/pages/publications/84876413292
UR - https://www.scopus.com/pages/publications/84876413292#tab=citedBy
U2 - 10.1007/s00210-013-0834-7
DO - 10.1007/s00210-013-0834-7
M3 - Article
C2 - 23338711
AN - SCOPUS:84876413292
SN - 0028-1298
VL - 386
SP - 311
EP - 318
JO - Naunyn-Schmiedeberg's Archives of Pharmacology
JF - Naunyn-Schmiedeberg's Archives of Pharmacology
IS - 4
ER -