Cargando…

Alpha-1 Antitrypsin Attenuates Acute Lung Allograft Injury in a Rat Lung Transplant Model

Ischemia-reperfusion injury (IRI) after lung transplantation triggers a cascade of inflammatory changes that can contribute to acute allograft injury. This influences both the short- and long-term survival of the lung allograft. Alpha-1 antitrypsin (AAT) is a protease inhibitor with known anti-infla...

Descripción completa

Detalles Bibliográficos
Autores principales: Emtiazjoo, Amir M., Hu, Hanbo, Lu, Li, Brantly, Mark L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer Health 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791593/
https://www.ncbi.nlm.nih.gov/pubmed/31723592
http://dx.doi.org/10.1097/TXD.0000000000000898
_version_ 1783459006035001344
author Emtiazjoo, Amir M.
Hu, Hanbo
Lu, Li
Brantly, Mark L.
author_facet Emtiazjoo, Amir M.
Hu, Hanbo
Lu, Li
Brantly, Mark L.
author_sort Emtiazjoo, Amir M.
collection PubMed
description Ischemia-reperfusion injury (IRI) after lung transplantation triggers a cascade of inflammatory changes that can contribute to acute allograft injury. This influences both the short- and long-term survival of the lung allograft. Alpha-1 antitrypsin (AAT) is a protease inhibitor with known anti-inflammatory and immune-regulatory properties that mitigate tissue damage. This study explores the protective effects of AAT in the setting of IRI utilizing a rat lung transplant model. METHODS. Orthotopic left single lung transplantation was performed from Lewis to Sprague-Dawley rats; recipients did not receive systemic immunosuppression. Before transplantation, the donor lungs were primed with either albumin (control) or AAT. Starting the day of transplantation, recipient rats also received either albumin (control) or AAT with subsequent doses administered over the next 7 days. On the eighth postoperative day, lung allografts were recovered and analyzed. RESULTS. Degree of inflammatory infiltrate, as quantified by the allograft weight (g)/body weight (kg) ratio, was significantly reduced in the AAT-treated group compared with controls (3.5 vs 7.7, respectively, P < 0.05). Treatment with AAT also significantly decreased allograft necrosis in treated animals, as measured by a semiquantitative score that ranged from 0 to 4 (1.25 vs 4, P < 0.05). In addition, lymphocytes isolated from recipients treatment group showed significant proliferative inhibition via a mixed lymphocyte response assay in response to donor antigens. CONCLUSIONS. AAT attenuates acute allograft injury and necrosis in a rat model of lung transplantation, suggesting that AAT may play a role in reducing IRI-induced inflammation.
format Online
Article
Text
id pubmed-6791593
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Wolters Kluwer Health
record_format MEDLINE/PubMed
spelling pubmed-67915932019-11-13 Alpha-1 Antitrypsin Attenuates Acute Lung Allograft Injury in a Rat Lung Transplant Model Emtiazjoo, Amir M. Hu, Hanbo Lu, Li Brantly, Mark L. Transplant Direct Basic Science Ischemia-reperfusion injury (IRI) after lung transplantation triggers a cascade of inflammatory changes that can contribute to acute allograft injury. This influences both the short- and long-term survival of the lung allograft. Alpha-1 antitrypsin (AAT) is a protease inhibitor with known anti-inflammatory and immune-regulatory properties that mitigate tissue damage. This study explores the protective effects of AAT in the setting of IRI utilizing a rat lung transplant model. METHODS. Orthotopic left single lung transplantation was performed from Lewis to Sprague-Dawley rats; recipients did not receive systemic immunosuppression. Before transplantation, the donor lungs were primed with either albumin (control) or AAT. Starting the day of transplantation, recipient rats also received either albumin (control) or AAT with subsequent doses administered over the next 7 days. On the eighth postoperative day, lung allografts were recovered and analyzed. RESULTS. Degree of inflammatory infiltrate, as quantified by the allograft weight (g)/body weight (kg) ratio, was significantly reduced in the AAT-treated group compared with controls (3.5 vs 7.7, respectively, P < 0.05). Treatment with AAT also significantly decreased allograft necrosis in treated animals, as measured by a semiquantitative score that ranged from 0 to 4 (1.25 vs 4, P < 0.05). In addition, lymphocytes isolated from recipients treatment group showed significant proliferative inhibition via a mixed lymphocyte response assay in response to donor antigens. CONCLUSIONS. AAT attenuates acute allograft injury and necrosis in a rat model of lung transplantation, suggesting that AAT may play a role in reducing IRI-induced inflammation. Wolters Kluwer Health 2019-05-29 /pmc/articles/PMC6791593/ /pubmed/31723592 http://dx.doi.org/10.1097/TXD.0000000000000898 Text en Copyright © 2019 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (http://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Basic Science
Emtiazjoo, Amir M.
Hu, Hanbo
Lu, Li
Brantly, Mark L.
Alpha-1 Antitrypsin Attenuates Acute Lung Allograft Injury in a Rat Lung Transplant Model
title Alpha-1 Antitrypsin Attenuates Acute Lung Allograft Injury in a Rat Lung Transplant Model
title_full Alpha-1 Antitrypsin Attenuates Acute Lung Allograft Injury in a Rat Lung Transplant Model
title_fullStr Alpha-1 Antitrypsin Attenuates Acute Lung Allograft Injury in a Rat Lung Transplant Model
title_full_unstemmed Alpha-1 Antitrypsin Attenuates Acute Lung Allograft Injury in a Rat Lung Transplant Model
title_short Alpha-1 Antitrypsin Attenuates Acute Lung Allograft Injury in a Rat Lung Transplant Model
title_sort alpha-1 antitrypsin attenuates acute lung allograft injury in a rat lung transplant model
topic Basic Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791593/
https://www.ncbi.nlm.nih.gov/pubmed/31723592
http://dx.doi.org/10.1097/TXD.0000000000000898
work_keys_str_mv AT emtiazjooamirm alpha1antitrypsinattenuatesacutelungallograftinjuryinaratlungtransplantmodel
AT huhanbo alpha1antitrypsinattenuatesacutelungallograftinjuryinaratlungtransplantmodel
AT luli alpha1antitrypsinattenuatesacutelungallograftinjuryinaratlungtransplantmodel
AT brantlymarkl alpha1antitrypsinattenuatesacutelungallograftinjuryinaratlungtransplantmodel