RT Journal Article
SR Electronic
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
FD European Respiratory Society
SP P850
VO 44
IS Suppl 58
A1 Michael Roth
A1 Daiana Stolz
A1 Eleni Papakonstantinou
A1 Ioannis Bonovolias
A1 George Karakiulakis
A1 Michael Tamm
YR 2014
UL http://erj.ersjournals.com/content/44/Suppl_58/P850.abstract
AB 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.