Preservation with α1 -antitrypsin improves primary graft function of murine lung transplants

The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation
Jessica GötzfriedDieter E Jenne

Abstract

Vascular damage and primary graft dysfunction increase with prolonged preservation times of transplanted donor lungs. Hence, storage and conservation of donated lungs in protein-free, dextran-containing electrolyte solutions, like Perfadex, is limited to about 6 hours. We hypothesized that transplanted lungs are protected against neutrophil-mediated proteolytic damage by adding α1-anti-trypsin (AAT), a highly abundant human plasma proteinase inhibitor, to Perfadex. A realistic clinically oriented murine model of lung transplantation was used to simulate the ischemia-reperfusion process. Lung grafts were stored at 4°C in Perfadex solution supplemented with AAT or an AAT mutant devoid of elastase-inhibiting activity for 18 hours. We examined wild-type and proteinase 3/neutrophil elastase (PR3/NE) double-deficient mice as graft recipients. Gas exchange function and infiltrating neutrophils of the transplanted lung, as well as protein content and neutrophil numbers in the bronchoalveolar lavage fluid, were determined. AAT as a supplement to Perfadex reduced the extent of primary graft dysfunction and early neutrophil responses after extended storage for 18 hours at 4°C and 4-hour reperfusion in the recipients. Double-knockout recip...Continue Reading

Citations

Mar 26, 2019·American Journal of Respiratory Cell and Molecular Biology·Natalia F Smirnova, Oliver Eickelberg
Nov 15, 2019·Transplantation Direct·Amir M EmtiazjooMark L Brantly
Aug 9, 2020·Frontiers in Cell and Developmental Biology·Danyang ZhengTao Li
Sep 25, 2019·Current Pulmonology Reports·Justin RosenheckEdward Cantu
Aug 8, 2021·International Journal of Molecular Sciences·Srinu TumparaSabina Janciauskiene

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Methods Mentioned

BETA
bronchoalveolar lavage
protein assay
bronchoalveolar

Software Mentioned

PeptideCutter
Cascleave
Prosper
GraphPad Prism

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