Increased alveolar soluble annexin v promotes lung inflammation and fibrosis

Susan Buckley, Wei Shi, Wei Xu, Mark R. Frey, Rex Moats, Annie Pardo, Moises Selman, David Warburton

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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-κβ 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.

Original languageEnglish (US)
Pages (from-to)1417-1429
Number of pages13
JournalEuropean Respiratory Journal
Volume46
Issue number5
DOIs
StatePublished - Nov 1 2015

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Annexins
Annexin A5
Pneumonia
Fibrosis
Idiopathic Pulmonary Fibrosis
Bronchoalveolar Lavage Fluid
Conditioned Culture Medium
Fibroblasts
Alveolar Epithelial Cells
Hydroxyproline
Receptor Protein-Tyrosine Kinases
Transforming Growth Factors
Mitogen-Activated Protein Kinases
Aerosols
Wound Healing
Cytokines

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Buckley, S., Shi, W., Xu, W., Frey, M. R., Moats, R., Pardo, A., ... Warburton, D. (2015). Increased alveolar soluble annexin v promotes lung inflammation and fibrosis. European Respiratory Journal, 46(5), 1417-1429. https://doi.org/10.1183/09031936.00002115

Increased alveolar soluble annexin v promotes lung inflammation and fibrosis. / Buckley, Susan; Shi, Wei; Xu, Wei; Frey, Mark R.; Moats, Rex; Pardo, Annie; Selman, Moises; Warburton, David.

In: European Respiratory Journal, Vol. 46, No. 5, 01.11.2015, p. 1417-1429.

Research output: Contribution to journalArticle

Buckley, S, Shi, W, Xu, W, Frey, MR, Moats, R, Pardo, A, Selman, M & Warburton, D 2015, 'Increased alveolar soluble annexin v promotes lung inflammation and fibrosis', European Respiratory Journal, vol. 46, no. 5, pp. 1417-1429. https://doi.org/10.1183/09031936.00002115
Buckley, Susan ; Shi, Wei ; Xu, Wei ; Frey, Mark R. ; Moats, Rex ; Pardo, Annie ; Selman, Moises ; Warburton, David. / Increased alveolar soluble annexin v promotes lung inflammation and fibrosis. In: European Respiratory Journal. 2015 ; Vol. 46, No. 5. pp. 1417-1429.
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