Lung Transplant Research Today is a free monthly online journal that collates and summarizes the latest research about Lung Transplant, including details on risks, prognosis, procedure, surgery, organ donation.

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

Liu H, Liu L, Fletcher BS, Visner GA

Department of Pediatrics, University of Florida,Gainesville, Florida, USA.

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.

Published 22 February 2006 in Am J Respir Crit Care Med, 173(5): 566-72.
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