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

PLoS One. 2023 May 30;18(5):e0285724. doi: 10.1371/journal.pone.0285724. eCollection 2023.

Abstract

Lung transplantation is the only curative option for end-stage chronic respiratory diseases. However the survival rate is only about 50% at 5 years. Although experimental evidences have shown that innate allo-responses impact on the clinical outcome, the knowledge of the involved mechanisms involved is limited. We established a cross-circulatory platform to monitor 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 dominant 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. This cross-circulation model allowed us to monitor the initial encounter between perfusing cells and the lung graft, in an easy, rapid, and controllable manner, to generate robust information on innate response and test targeted therapies for improvement of lung transplantation outcome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Genes, MHC Class II
  • Lung
  • Lung Transplantation*
  • Perfusion
  • Swine

Grants and funding

ES received funding from Association Chirurgicale Pour Le Développement et L'Amélioration des Techniques de Dépistage et de Traitement des Maladies Cardio-vasculaires (ADETEC-Coeur) and from la « Chaire Universitaire de Transplantation Université de Versailles-Saint-Quentin en Yvelines, Hôpital Foch et Fondation Foch, AR received a grant from the Association Gregory Lemarchal and the association Vaincre la Mucoviscidose (project number RF20220503016) and ISC received funding from INRAE institutional support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.