Wellcome Trust Clinical PhD Programme at Imperial College London: 'The critical role of lung-marginated monocytes in transplant-associated acute lung injury'. (360G-Wellcome-097471_Z_11_Z)

Acute lung injury (ALI) within the lung transplantation paradigm is a major cause of rejection of potential donor organs and graft dysfunction in recipients. A combination of donor lung inflammation (DLI) in addition to ischaemia-reperfusion exposure is now considered responsible for its limited success. We hypothesise that DLI has a substantial impact on transplant-related ALI, and specifically that monocytes marginated within the microvasculature of the donor lungs interact with the pulmonary endothelium and play a key role in its pathogenesis. We have established an ex vivo model of DLI, utilising a mouse isolated perfused lung (IPL) preparation which provides an intact whole organ system without systemic influence. We aim to: 1. Profile the role of lung-marginated monocytes in DLI and their contribution to transplant-associated ALI utilising the ex vivo IPL and monocyte depletion techniques 2. Investigate the precise molecular mechanisms of monocyte-endothelial interactions utilising temporal chimaeras in in vitro co-culture and ex vivo IPL 3. Relate our findings to the clinical paradigm by investigating human lung transplant samples The results of this work will provide important insights into mechanisms and potential therapeutic avenues, in DLI and lung transplantation, positively impacting on the success of this procedure.