title: NDP-MSH inhibits neutrophil migration through nicotinic and adrenergic receptors in experimental peritonitis.
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.
authors: Department of Pharmacology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Av. Bandeirantes 3900, Ribeirão Preto, São Paulo, Brazil.
authors: Jozi
authors: J
authors: Figueiredo
authors: Ana Elisa
authors: AE
authors: Ferreira
authors: Rangel Leal
authors: RL
authors: Silva
authors: Luis
authors: L
authors: Ulloa
authors: Paolo
authors: P
authors: Grieco
authors: Thiago Mattar
authors: TM
authors: Cunha
authors: Sérgio Henrique
authors: SH
authors: Ferreira
authors: Fernando de Queiróz
authors: Fde Q
authors: Cunha
authors: Alexandre
authors: A
authors: Kanashiro
mesh_terms: D000818:Animals; D002351:Carrageenan; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D054426:Chemokine CXCL2 / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D036904:Leukocyte Rolling / Q000187:drug effects; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D010538:Peritonitis / Q000139:chemically induced / Q000276:immunology*; D011941:Receptors, Adrenergic / Q000502:physiology; D011978:Receptors, Nicotinic / Q000502:physiology; D000521:alpha-MSH / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D016207:Cytokines; D011941:Receptors, Adrenergic; D011978:Receptors, Nicotinic; D000521:alpha-MSH; C027756:MSH, 4-Nle-7-Phe-alpha-; D002351:Carrageenan