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The α-MSH/MCR axis in the immuno-pathogenesis of allergic bronchial asthma
Wegmann M 1 , Webering S 2 , Lunding L 1 , Fehrenbach H 2
1
Division of Mouse Models of Asthma; 2 Division of Experimental Pneumology, Priority Area Asthma &
Allergy, Research Center Borstel, Airway Research Center North, Member of the German Center for
Lung Research
The phenotype of allergic bronchial asthma arises from a chronic inflammation of the airways.
Following the hygiene hypothesis a predominant T helper 2 (TH2) type immune response appears to
be of significant importance for the initiation of this inflammation. However, the mechanisms
underlying progression and chronification of the allergic immune-response in asthmatic airways are
not fully understood, but imply permanent release of pro-inflammatory mediators triggered by allergen
inhalation. This in turn overwhelms inherent regulatory feed-back loops that typically control
inflammatory reactions by the release of anti-inflammatory factors. One of these mediators could be α
melanocyte-stimulating hormone (α-MSH), which has been described to reduce inflammation in
several dermatologic and neurologic disorders. The present study aimed at elucidating the role of α-
MSH in the asthmatic lung.
In different mouse models of experimental allergic asthma we found that α-MSH is produced in
inflamed airways and that the amount of α-MSH released into the broncho-alveolar lumen rises with
increasing degree and duration of allergic airway inflammation. Besides alveolar macrophages α-MSH
is mainly produced by the airway epithelium. From the five melanocortin receptors (MC-R) that have
been identified so far, only MC5-R is expressed in healthy animals, mainly by alveolar macrophages
and airway epithelial cells. In animals with experimental asthma, MC5-R expression could be further
observed in infiltrating eosinophils. Additionally, we detected expression of MC1-R by infiltrating
neutrophils and fibroblasts in the tunica adventitia of inflamed vessels.
These data suggest a central role of the airway epithelium in regulating the allergic immune response
in asthmatic airways by releasing the anti-inflammatory factor α-MSH.
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