Regulation of melanocortin 1 receptor in allergic rhinitis in vitro and in vivo

Clin Exp Allergy. 2016 Aug;46(8):1066-74. doi: 10.1111/cea.12759. Epub 2016 Jun 15.

Abstract

Background: α-melanocyte-stimulating hormone (α-MSH) was shown to inhibit allergic airway inflammation and exert suppressive effects on human basophils.

Objective: This study aims to extend our current knowledge on the melanocortin 1 receptor (MC1R) expression in nasal tissue of patients with allergic rhinitis (AR) and functional effects of α-MSH in human basophils especially from patients with allergic rhinitis.

Methods: MC1R expression before and after nasal allergen provocation was studied in nasal mucosal tissue of AR patients and in a mouse model of allergic airway inflammation using immunofluorescence. In vitro regulation of the MC1R and CD203c surface expression on whole-blood basophils of patients with AR and controls was assessed with flow cytometry. Functional effects of α-MSH on isolated basophils were analysed regarding apoptosis with flow cytometry and chemotaxis using a Boyden chamber assay.

Results: We detected an accumulation of MC1R-positive basophils in nasal mucosa tissue of patients with AR 24 h after nasal allergen provocation. Such accumulation was not present in mucosa sections from healthy controls. In mice with allergic airway inflammation, we found a clear accumulation of MC1R-positive basophils in the nasal tissue compared to control mice. MC1R expression was inducible in AR patients and controls by stimulation with anti-IgE. α-MSH inhibited anti-IgE and grass pollen induced upregulation of CD203c, but had no effect on chemotaxis or apoptosis of basophils in vitro.

Conclusions and clinical relevance: MC1R-positive basophils accumulate in the nasal mucosa of patients with AR after nasal allergen provocation. Since α-MSH suppresses proinflammatory effector functions in human basophils via the MC1R, it constitutes an interesting novel target for modulating the allergic inflammatory response.

Keywords: allergic rhinitis; alpha-melanocyte stimulating hormone; basophils; melanocortin receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Allergens / immunology
  • Animals
  • Basophils / immunology
  • Basophils / metabolism
  • Biopsy
  • Chemotaxis / immunology
  • Disease Models, Animal
  • Female
  • Gene Expression
  • Humans
  • Immunoglobulin E / immunology
  • Male
  • Mice
  • Nasal Mucosa / immunology
  • Nasal Mucosa / metabolism
  • Nasal Mucosa / pathology
  • Nasal Provocation Tests
  • Phosphoric Diester Hydrolases / metabolism
  • Pollen / immunology
  • Pyrophosphatases / metabolism
  • Receptor, Melanocortin, Type 1 / genetics
  • Receptor, Melanocortin, Type 1 / metabolism*
  • Respiratory Function Tests
  • Rhinitis, Allergic / diagnosis
  • Rhinitis, Allergic / genetics
  • Rhinitis, Allergic / immunology*
  • Rhinitis, Allergic / metabolism*
  • Skin Tests
  • Young Adult
  • alpha-MSH / metabolism

Substances

  • Allergens
  • ENPP3 protein, human
  • Receptor, Melanocortin, Type 1
  • Immunoglobulin E
  • alpha-MSH
  • Phosphoric Diester Hydrolases
  • Pyrophosphatases