Rationale. Cholinergic parasympathetic system via the release of acetylcholine (ACh) is a major regulator of airway function but its role in asthma remodelling is unknown. Aim of this study was to evaluate the expression of cholinergic M3 muscarinic receptors (M3R) in relation to vascular, matrix and neural remodelling markers in mild and severe asthma.
Methods. M3R, angiogenin, NGF and procollagen III were analysed by immunohistochemistry in cryostat sections of healthy controls (n=8), mild (n=15) and severe (n=15) asthmatics. Co-localisation of CD31+ (endothelial) and M3R+ cells was evaluated by confocal immunofluorescence. Human bronchial primary fibroblast (HBPF) cultures of controls and asthmatics stimulated with acetylcholine were immunostained for M3R.
Results. In bronchial lamina propria the number of M3R+, angiogenin+, NGF+ cells were higher in severe compared to mild asthmatics and controls (M3R: p<0,01; angiogenin: p<0.05 and p<0.001; NGF: p<0.05 and p<0.001, respectively). Procollagen III was more expressed in severe asthmatics compared to controls (p<0,05). M3R+ cells were related negatively to FEV1 and positively to angiogenin+ and NGF+ cells (p<0.05) in asthmatics. Confocal analysis demonstrated that CD31+ cells co-localised with M3R. In HBPF of healthy controls and asthmatics acetylcholine increased M3R expression.
Conclusions. The results of the study shed light on the role of M3 receptors in the different aspects of asthma remodelling.