Abstract
Introduction: Activin A is implicated in the remodeling processes. It exerts its biological effects though activation of transmembrane serine/threonine kinase receptors.
Aim: To investigate both Activin A BAL levels and receptors' staining and to determine whether any upregulated expression is implicated in the remodeling processes.
Methods: 12 patients with Severe Refractory [SRA] and 11 with mild to moderate disease were studied. All subjects underwent bronchoscopy. In BAL activin-A, cell counts, IL-8, TGF-β1, ECP and IL-13, were assessed. Smooth muscle area (SMA), reticular basement membrane (RBM) thickness and the length of epithelial detachment (ED) in bronchial biopsies of asthmatics with different underlying severity were assessed. Biopsies were stained with antibodies for ActRIIΑ, ActIIB and ALK-4. Possible associations with inflammatory cells and mediators in BAL were also assessed. All sections were analyzed with image analysis.
Results: Activin-A was significantly increased in BAL of patients with SRA compared to mild and moderate ones [median IQR, 193 (87-264) vs 35(22-93), p<0.001]. Using regression analysis a positive association between Activin-A increased SMA, ED and levels of IL-13 were observed. ALK-4 receptor was highly expressed in patients with SRA compared to mild to moderate ones.
Conclusions: ALK-4 seems to be the major receptor for Activin-A signaling in airway epithelium. Activin-A is implicated in the remodeling process in patients with SRA.
- Copyright ©ERS 2015
