Regulation of melanocortin 1 receptor in allergic rhinitis in vitro and in vivo.
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.
['Kleiner|S|S|', 'Braunstahl|G-J|GJ|', 'Rüdrich|U|U|', 'Gehring|M|M|', 'Eiz-Vesper|B|B|', 'Luger|T A|TA|', 'Steelant|B|B|', 'Seys|S F|SF|', 'Kapp|A|A|', 'Böhm|M|M|', 'Hellings|P W|PW|', 'Raap|U|U|']
D000328:Adult D000485:Allergens D000818:Animals D001491:Basophils D001706:Biopsy D002633:Chemotaxis D004195:Disease Models, Animal D005260:Female D015870:Gene Expression D006801:Humans D007073:Immunoglobulin E D008297:Male D051379:Mice D009297:Nasal Mucosa D009299:Nasal Provocation Tests D010727:Phosphoric Diester Hydrolases D011058:Pollen D011755:Pyrophosphatases D044102:Receptor, Melanocortin, Type 1 D012129:Respiratory Function Tests D065631:Rhinitis, Allergic D012882:Skin Tests D055815:Young Adult D000521:alpha-MSH
allergic rhinitis basophils alpha-melanocyte stimulating hormone melanocortin receptor