A cross-circulatory platform for monitoring innate responses in lung grafts

Abstract

Lung transplantation is the only curative option of end-stage chronic respiratory diseases. However the survival rate is only about 50% at 5 years. Whereas experimental evidences support that innate allo-responses impact on the clinical outcome, the knowledge of the involved mechanisms is limited. Here, we evaluate a cross-circulatory platform for monitoring the early recruitment and activation of immune cells in an extracorporeal donor lung by coupling blood perfusion to cell mapping with a fluorescent marker in the pig, a commonly-used species for lung transplantation. The perfusing pig cells were easily detectable in lung cell suspensions, in broncho-alveolar lavages and in different areas of lung sections, indicating infiltration of the organ. Myeloid cells (granulocytes and monocytic cells) were the dominantly recruited subsets. Between 6 and 10 h of perfusion, recruited monocytic cells presented a strong upregulation of MHC class II and CD80/86 expression, whereas alveolar macrophages and donor monocytic cells showed no significant modulation of expression. Altogether the cross-circulation model permits to monitor the initial encounter between perfusing cells and lung graft, in an easy, rapid, and controllable manner, for generating robust information on innate response and testing targeted therapies for improvement of lung transplantation outcome.