Muscarinic M^sub 3^ Receptors Contribute to Allergen-Induced Airway Remodeling in Mice

This paper aims to study the contribution of the muscarinic M3 receptor to allergen-induced remodeling using muscarinic M3 receptor subtype-deficient (M3R^sup -/-^) mice. Wild-type (WT), M1R^sup -/-^, and M2R^sup -/-^ mice were used as controls. C57Bl/6 mice were sensitized and challenged with ovalbumin. Control animals were challenged with saline. Allergen exposure induced goblet cell metaplasia, airway smooth muscle thickening (1.7-fold), pulmonary vascular smooth muscle remodeling (1.5-fold), and deposition of collagen I (1.7-fold) and fibronectin (1.6-fold) in the airway wall of WT mice. These effects were absent or markedly lower in M3R^sup -/-^ mice (30%-100%), whereas M1R^sup -/-^ and M2R^sup -/-^ mice responded similarly to WT mice. Interestingly, allergen-induced airway inflammation, assessed as infiltrated eosinophils and T helper type 2 cytokine expression, was similar or even enhanced in M3R^sup -/-^ mice. The data indicate that acetylcholine contributes to allergen-induced remodeling and smooth muscle mass via the muscarinic M3 receptor, and not via M1 or M2 receptors.