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

Author(s)

Figueiredo, Jozi ^[1] ; Ferreira, Ana Elisa ^[1] ; Silva, Rangel Leal ^[1] ; Ulloa, Luis ^[2] ; Grieco, Paolo ^[3] ; Cunha, Thiago Mattar ^[1] ; Ferreira, Sergio Henrique ^[1] ; Cunha, Fernando de Queiroz ^[1] ; Kanashiro, Alexandre ^[1]

Affiliation

^[1] Univ Sao Paulo, Dept Pharmacol, Fac Med Ribeirao Preto, BR-14049 90 Sao Paulo - Brazil

^[2] UMDNJ New Jersey Med Sch, Dept Surg, Lab Antiinflammatory Signaling & Surg Immunol, Newark, NJ 07103 - USA

^[3] Univ Naples Federico II, Dept Pharmaceut & Toxicol Chem, I-80131 Naples - Italy

• Document type: Journal article
• Source: NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY; v. 386, n. 4, p. 311-318, APR 2013.
• Web of Science Citations: 7

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. (AU)

• FAPESP's process: 12/04237-2 - Antiinflammatory Cholinergic Pathway: The role of neuroimmunomodulation in the control of inflammatory response.
• Grantee: Alexandre Kanashiro
• Support Opportunities: Scholarships in Brazil - Young Researchers
• FAPESP's process: 11/11931-0 - Research potassium channel voltage-dependent induction and maintenance of persistent and neuropathic hypernociception.
• Grantee: Jozi Godoy Figueiredo
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 11/20343-4 - Antiinflammatory cholinergic pathway: the role of neuroimmunomodulation in the control of inflammatory response
• Grantee: Alexandre Kanashiro
• Support Opportunities: Research Grants - Young Investigators Grants