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Novel action of indoleamine 2,3-dioxygenase attenuating acute lung allograft injury.

Abstract：

RATIONALE:Lung allografts are prone to reperfusion injury and acute rejection, which, in addition to infiltrating lymphocytes, are accompanied by neutrophil infiltration and neutrophil-associated oxidative stress. Indoleamine 2,3-dioxygenase (IDO) is a unique cytosolic enzyme that possesses T-cell-suppressive and antioxidant properties. OBJECTIVES:The purpose of this study was to determine if genetic up-regulation of IDO could ameliorate acute lung allograft injury. METHODS:Lung orthotopic transplants were performed using Lewis donors and Sprague-Dawley rat recipients (allografts) or the same strain (isografts). Plasmid-encoding human IDO was delivered to donor lungs in vivo using a nonviral gene-transfer vector, polyethylenimine. Transplanted lungs were evaluated at 6 d post-transplantation based on pulmonary function, histology, inflammatory responses, and their associated oxidative stress. Basic biology of the IDO-overexpressing lung cells was evaluated in vitro in response to external oxidant. MEASUREMENTS AND MAIN RESULTS:This gene delivery method led to uniform transgene expression in lung tissue distributed in airway, alveolar epithelial, and endothelial cells. IDO overexpression in lung allografts resulted in a significant protective effect with improvement in functional properties (peak airway pressure and oxygenation) and histologic appearance. Although IDO was able to block local T-cell responses, it failed to abrogate neutrophilic infiltration and the inflammation-associated oxidative stress. IDO-enhanced lung cells were resistance to oxidant-induced necrosis and apoptosis by limiting intracellular reactive oxygen species formation. CONCLUSIONS:These results demonstrate that IDO prevents acute lung allograft injury through augmenting the local antioxidant defense system and inhibiting alloreactive T-cell responses.

journal_name

Am J Respir Crit Care Med

journal_title

American journal of respiratory and critical care medicine

authors

Liu H,Liu L,Fletcher BS,Visner GA

doi

10.1164/rccm.200509-1413OC

keywords:

subject

Has Abstract

pub_date

2006-03-01 00:00:00

pages

566-72

issue

eissn

1073-449X

issn

1535-4970

pii

200509-1413OC

journal_volume

173

pub_type

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Novel action of indoleamine 2,3-dioxygenase attenuating acute lung allograft injury.