Donor Leukocyte Trafficking and Damage-associated Molecular Pattern Expression During Ex Vivo Lung Perfusion.

Abstract

Background:While ex vivo lung perfusion (EVLP) has become established in lung transplantation, the cellular processes occurring during this period are not yet fully understood. Prior studies demonstrated that donor leukocytes (DLs) migrate from the graft into the perfusate during EVLP, but the distribution of DLs in graft and perfusate compartments has not been characterized. Moreover, cell death of DLs has been implicated in mediating graft injury during EVLP, but the underlying mechanisms have not been elucidated. We hypothesized the following: (1) there is a nonspecific migration of DLs from the graft into perfusate and (2) cell death of DLs releases damage-associated molecular patterns (DAMPs) that contribute to the inflammatory milieu during EVLP. Methods:EVLP was performed on rat lungs for 3 hours (N = 6). At the end of EVLP, flow cytometry was used to quantify the distribution of different DL cell types in both the graft and perfusate compartments. During EVLP, the perfusate was also sampled hourly to measure levels of DAMPs and downstream inflammatory cytokines generated during EVLP. Results:At the conclusion of EVLP, there was a significantly higher proportion of T and B cells present in the perfusate compartment compared with the graft compartment. There was a time-dependent increase in extracellular DNA and tumor necrosis factor α in the perfusate during EVLP. Conclusions:T cells and B cells are enriched in the perfusate compartment during EVLP. Cell death of DLs contributes to an accumulation of DAMPs during EVLP.

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Published Version (Please cite this version)

10.1097/TXD.0000000000000968

Publication Info

Davis, Robert P, John Yerxa, Qimeng Gao, Jared Gloria, Uwe Scheuermann, Mingqing Song, Min Zhang, William Parker, et al. (2020). Donor Leukocyte Trafficking and Damage-associated Molecular Pattern Expression During Ex Vivo Lung Perfusion. Transplantation Direct, 6(3). p. e532. 10.1097/TXD.0000000000000968 Retrieved from https://hdl.handle.net/10161/20615.

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Hartwig

Matthew Hartwig

Professor of Surgery

Dr. Hartwig is a thoracic surgeon with a clinical focus in lung transplantation and robotic assisted minimally invasive thoracic surgery for the treatment of diseases of the chest.  He serves as the Surgical Director of the Duke Lung Transplant Program and the Esophageal Center at Duke.  Additionally, he directs the Surgical Office of Clinical Research, which manages the clinical research portfolio for the Department of Surgery.  He also leads a successful program of clinical, basic and translational research in thoracic surgery and lung transplantation. He currently directs the Duke Ex Vivo Organ Laboratory (DEVOL), is the Chief of Lung Transplant Research, and is a faculty member at the Duke Clinical Research Institute (DCRI).

Dr. Hartwig has over 150 peer reviewed publications, received numerous awards, chaired many sessions at national and international meetings, serves regularly on NIH study sections, and is on the editorial board of many prominent journals. He has also personally mentored over pre-and post-doctoral trainees, many of whom are now engaged in their own successful research careers.

Barbas

Andrew Serghios Barbas

Associate Professor of Surgery

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