PT - JOURNAL ARTICLE AU - Mallory Pain AU - Pierre-Joseph Royer AU - Jennifer Loy AU - Maxime Fieux AU - Adrien Tissot AU - Philippe Lacoste AU - Damien Reboulleau AU - Sandie Parès AU - Karine Botturi AU - Antoine Magnan AU - COLT Consortium TI - A new biomarker for chronic lung allograft dysfunction DP - 2014 Sep 01 TA - European Respiratory Journal PG - 1425 VI - 44 IP - Suppl 58 4099 - http://erj.ersjournals.com/content/44/Suppl_58/1425.short 4100 - http://erj.ersjournals.com/content/44/Suppl_58/1425.full SO - Eur Respir J2014 Sep 01; 44 AB - Introduction : Chronic lung allograft dysfunction (CLAD) is the major limitation to lung transplantation. Bronchial epithelial cells (BEC) seem to play a key role and several studies suggest their implication through epithelial to mesenchymal transition (EMT). The aim of this study was to set up in vitro model of co-culture for testing the impact of allogenic context on EMT in order to discover new biomarkers predictive of CLAD.Methods : Primary bronchial epithelial cells (PBECs) were cultured with activated T cells and monocytes from healthy patients during 4 days. Epithelial and mesenchymal markers were assessed by qPCR and western blot and secretion of cytokines was measured in culture supernatants. Potential biomarkers were assayed in plasma from CLAD and stable lung transplant recipients from the COLT cohort.Results :Activated T cells and monocytes co-cultured with PBECs in presence of TGF-β1 had no effect on junction expression (E-cadherin, ZO-1), but increased fibronectin expression (n=4 p<0.05) and MMP-9 secretion (p<0.01). MCP-1 and CXCL-10 secretion were increased in supernatants (n=8 p<0,05). MCP-1 increased PBECs MMP-9 expression (p<0.05) and treatment of co-culture with anti-CCR2 (MCP-1 receptor) reduced MMP-9 expression and secretion (n=4 p<0,005). Plasmatic levels of MMP-9 increased were in CLAD patients compared to controls, and were already increased 6 months before diagnosis.Conclusion :This new in vitro model suggests the implication of immune cells in airway remodeling by the induction of extracellular matrix marker and suggest a link between MCP-1 and MMP-9. It appears as a relevant tool for biomarker discovery. Plasmatic MMP-9 secretion may be a valuable biomarker for CLAD.