BACKGROUND: Lung graft dysfunction and rejection are significant causes of morbidity and mortality in transplant recipients. Thioredoxin-1, a redox-regulatory protein, functions as an antioxidant in multiple organs, including lungs. We examined whether priming of the donor lungs with thioredoxin-1 before transplantation attenuates acute lung injury. METHODS: Orthotopic left lung transplantation was performed from Lewis (donor) to Sprague-Dawley (recipient) rats. Donor lungs were perfused and stored in Perfadex solution (Vitrolife, Uppsala, Sweden), with or without purified thioredoxin-1. Changes in bronchoalveolar lavage (BAL) analysis, allograft oxygen exchange function, nuclear factor kappaB (NF-kappaB)/DNA binding, myeloperoxidase activities, and immunohistologic evaluation of neutrophils, macrophages, and cytotoxic T-cells (CD8(+)) infiltration were examined in post-transplant allograft (left) and native (right) lungs at Days 1 and 5. RESULTS: BAL cell differential analysis showed significant increases in macrophages and neutrophils in allografts at Day 1 post-transplant. At Days 1 and 5, lymphocyte infiltration was significantly increased and myeloperoxidase and NF-kappaB/DNA binding activities were increased vs basal activities. Immunohistology staining revealed increased infiltration of macrophages, neutrophils, and CD8(+) T cell sub-sets. Pre-transplant priming of donor lungs with thioredoxin-1 improved oxygen exchange and attenuated NF-kappaB/DNA binding activity, and infiltration of macrophages, neutrophils, and CD8(+) T cell sub-sets in allografts at Days 1 and 5 post-transplant. CONCLUSIONS: Priming of donor lungs with thioredoxin-1 before transplant attenuates acute allograft injury in a rat model of lung transplantation, and appears to be associated with the antioxidant function of thioredoxin-1 that limits early ischemia-reperfusion injury, NF-kappaB activation, and progressive infiltration of inflammatory and immune cells in allografts.
BACKGROUND: Lung graft dysfunction and rejection are significant causes of morbidity and mortality in transplant recipients. Thioredoxin-1, a redox-regulatory protein, functions as an antioxidant in multiple organs, including lungs. We examined whether priming of the donor lungs with thioredoxin-1 before transplantation attenuates acute lung injury. METHODS: Orthotopic left lung transplantation was performed from Lewis (donor) to Sprague-Dawley (recipient) rats. Donor lungs were perfused and stored in Perfadex solution (Vitrolife, Uppsala, Sweden), with or without purified thioredoxin-1. Changes in bronchoalveolar lavage (BAL) analysis, allograft oxygen exchange function, nuclear factor kappaB (NF-kappaB)/DNA binding, myeloperoxidase activities, and immunohistologic evaluation of neutrophils, macrophages, and cytotoxic T-cells (CD8(+)) infiltration were examined in post-transplant allograft (left) and native (right) lungs at Days 1 and 5. RESULTS: BAL cell differential analysis showed significant increases in macrophages and neutrophils in allografts at Day 1 post-transplant. At Days 1 and 5, lymphocyte infiltration was significantly increased and myeloperoxidase and NF-kappaB/DNA binding activities were increased vs basal activities. Immunohistology staining revealed increased infiltration of macrophages, neutrophils, and CD8(+) T cell sub-sets. Pre-transplant priming of donor lungs with thioredoxin-1 improved oxygen exchange and attenuated NF-kappaB/DNA binding activity, and infiltration of macrophages, neutrophils, and CD8(+) T cell sub-sets in allografts at Days 1 and 5 post-transplant. CONCLUSIONS: Priming of donor lungs with thioredoxin-1 before transplant attenuates acute allograft injury in a rat model of lung transplantation, and appears to be associated with the antioxidant function of thioredoxin-1 that limits early ischemia-reperfusion injury, NF-kappaB activation, and progressive infiltration of inflammatory and immune cells in allografts.
Authors: S D Ross; I L Kron; J J Gangemi; K S Shockey; M Stoler; J A Kern; C G Tribble; V E Laubach Journal: Am J Physiol Lung Cell Mol Physiol Date: 2000-09 Impact factor: 5.464
Authors: Andrew E Gelman; Andrew J Fisher; Howard J Huang; Maher A Baz; Ciara M Shaver; Thomas M Egan; Micheal S Mulligan Journal: J Heart Lung Transplant Date: 2017-07-24 Impact factor: 10.247