RT Journal Article
SR Electronic
T1 Increased alveolar soluble annexin V promotes lung inflammation and fibrosis
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP ERJ-00021-2015
DO 10.1183/09031936.00002115
A1 Susan Buckley
A1 Wei Shi
A1 Wei Xu
A1 Mark R. Frey
A1 Rex Moats
A1 Annie Pardo
A1 Moises Selman
A1 David Warburton
YR 2015
UL http://erj.ersjournals.com/content/early/2015/07/09/09031936.00002115.abstract
AB The causes underlying the self-perpetuating nature of idiopathic pulmonary fibrosis (IPF), a progressive and usually lethal disease, remain unknown. We hypothesised that alveolar soluble annexin V contributes to lung fibrosis, based on the observation that human IPF bronchoalveolar lavage fluid (BALF) containing high annexin V levels promoted fibroblast involvement in alveolar epithelial wound healing that was reduced when annexin V was depleted from the BALF.Conditioned medium from annexin V-treated alveolar epithelial type 2 cells (AEC2), but not annexin V per se, induced proliferation of human fibroblasts and contained pro-fibrotic, IPF-associated proteins, as well as pro-inflammatory cytokines that were found to correlate tightly (r>0.95) with annexin V levels in human BALF. ErbB2 receptor tyrosine kinase in AECs was activated by annexin V, and blockade reduced the fibrotic potential of annexin V-treated AEC-conditioned medium. In vivo, aerosol delivery of annexin V to mouse lung induced inflammation, fibrosis and increased hydroxyproline, with activation of Wnt, transforming growth factor-β, mitogen-activated protein kinase and nuclear factor-κB signalling pathways, as seen in IPF.Chronically increased alveolar annexin V levels, as reflected in increased IPF BALF levels, may contribute to the progression of IPF by inducing the release of pro-fibrotic mediators.Soluble annexin V, found at increased levels in BALF from IPF patients, promotes inflammation and fibrosis in mouse lung http://ow.ly/MHobz