RT Journal Article
SR Electronic
T1 Activin-A expression is increased in severe asthma and is involved in tissue angiogenesis
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P2313
VO 40
IS Suppl 56
A1 Konstantinos Samitas
A1 Eleftherios Zervas
A1 Nikolaos Poulos
A1 Maria Semitekolou
A1 Stelios Vittorakis
A1 Harsha Kariyawasam
A1 Vily Panoutsakopoulou
A1 Georgina Xanthou
A1 Mina Gaga
YR 2012
UL http://erj.ersjournals.com/content/40/Suppl_56/P2313.abstract
AB Background: Our recent studies show that Activin-A (Act-A), a cytokine belonging to the TGF-β superfamily, suppresses mouse allergic responses; however its effects on human asthma remain unknown.Objectives: To determine Act-A expression in healthy controls (CTRL) and asthmatics, identify its cellular sources and signaling mediators, and examine correlations with disease severity and airway remodelling.Methods: Serum samples were obtained from 46 mild-to-moderate asthmatics (MMA), 27 severe asthmatics (SA) and 41 CTRL. 55 subjects (18 CTRL, 18 MMA, 19 SA) underwent bronchoscopy with endobronchial biopsy and BALF collection. Act-A levels in the serum/BALF were examined. Expression of Act-A and its principal signaling mediator ALK4 in the bronchial tissue were assessed by confocal microscopy. Basement membrane thickness, goblet cell hyperplasia and angiogenesis (vessels/mm2) were also determined.Results: Act-A levels were significantly increased in MMA in the serum and in MMA and SA in BALF. Serum Act-A was further increased during asthma exacerbation. Bronchial tissue Act-A expression was significantly increased in asthmatics, especially in the subepithelium in SA, while ALK-4 expression decreased with disease severity. Act-A was mainly expressed by mast cells, neutrophils, macrophages and smooth muscle cells. Act-A and ALK-4 were also localized in endothelial cells, particularly in SA. Subepithelial Act-A expression correlated with angiogenesis and disease severity.Conclusions: Our data suggest that Act-A plays a crucial role in asthma inflammation and participates in the regulation of angiogenesis in SA. Ongoing in vitro studies will further elucidate its specific role.