TY - JOUR T1 - Secretion of hyaluronic acid is mediated by muscarinic receptors in airway smooth muscle cells of patients with COPD JF - European Respiratory Journal JO - Eur Respir J VL - 44 IS - Suppl 58 SP - P850 AU - Michael Roth AU - Daiana Stolz AU - Eleni Papakonstantinou AU - Ioannis Bonovolias AU - George Karakiulakis AU - Michael Tamm Y1 - 2014/09/01 UR - http://erj.ersjournals.com/content/44/Suppl_58/P850.abstract N2 - BACKGROUND: Airway smooth muscle cells (ASMCs) of patients with COPD exhibit abnormal metabolism of hyaluronic acid (HA), contributing to inflammation and remodeling of the lung.AIM: To investigate if the abnormal metabolism of HA in ASMC is mediated by muscarinic receptors.METHODS: HA was measured in the BAL of COPD patients at a stable state (n=53) and at exacerbation (n=44). ASMC were established from endobronchial biopsies of COPD and control. Cells were treated with carbachol and secretion of HA was measured by ELISA. Gene expression of HA synthases (HAS), hyaluronidases and HA receptors was investigated by qPCR.RESULTS: HA was significantly increased in the BAL of exacerbated patients as compared to stable COPD patients (p<0.005). HA secretion by ASMC was significantly stimulated by carbachol by 350% in COPD (p<0.001) and by 60% in controls (p<0.005). Carbachol also resulted in a significant increase of HAS-2 gene expression by 3 fold in COPD (p<0.005) and by 2 fold in controls.CONCLUSIONS: Increased levels of HA in BAL are associated with acute exacerbations in COPD. This may be attributed to stimulation of muscarinic receptor in ASMC, apparently mediated by increased gene expression of HAS-2. Our results strengthen the concept for the pathologic HA turnover in COPD and the beneficial effect of targeting muscarinic receptors in the treatment of the disease. ER -