Onset of Inflammation With Ischemia: Implications for Donor Lung Preservation and Transplant Survival

• Published in: American journal of transplantation Vol. 16; no. 9; pp. 2598 - 2611
• Main Authors: Tao, J.‐Q., Sorokina, E. M., Vazquez Medina, J. P., Mishra, M. K., Yamada, Y., Satalin, J., Nieman, G. F., Nellen, J. R., Beduhn, B., Cantu, E., Habashi, N. M., Jungraithmayr, W., Christie, J. D., Chatterjee, S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Limited 01-09-2016
• Subjects: adhesion molecules/integrins; Advanced glycosylation end products; Animals; basic (laboratory) research/science; Blood flow; Cell adhesion molecules; Endothelium; Glycosylation; Graft Rejection - prevention & control; Graft Survival; Humans; Hypoxia; Incidence; Inflammation; Inflammation - epidemiology; Inflammation Mediators - metabolism; Ischemia; Ischemia - physiopathology; Lipid Peroxidation; Lung - physiopathology; Lung Transplantation; lung transplantation/pulmonology; Lungs; Mice; Organ Preservation - methods; Parenchyma; Pattern recognition receptors; Preservation; Reactive oxygen species; Reactive Oxygen Species - metabolism; Rodents; Signal Transduction; signaling/signaling pathways; Surgery; Tissue Donors; translational research/science; adhesion molecules/integrins; translational research/science; signaling/signaling pathways; lung transplantation/pulmonology; basic (laboratory) research/science
• ISSN: 1600-6135; 1600-6143; 1600-6143
• DOI: 10.1111/ajt.13794

Lungs stored ahead of transplant surgery experience ischemia. Pulmonary ischemia differs from ischemia in the systemic organs in that stop of blood flow in the lung leads to loss of shear alone because the lung parenchyma does not rely on blood flow for its cellular oxygen requirements. Our earlier studies on the ischemia‐induced mechanosignaling cascade showed that the pulmonary endothelium responds to stop of flow by production of reactive oxygen species (ROS). We hypothesized that ROS produced in this way led to induction of proinflammatory mediators. In this study, we used lungs or cells subjected to various periods of storage and evaluated the induction of several proinflammatory mediators. Isolated murine, porcine and human lungs in situ showed increased expression of cellular adhesion molecules; the damage‐associated molecular pattern protein high‐mobility group box 1 and the corresponding pattern recognition receptor, called the receptor for advanced glycation end products; and induction stabilization and translocation of hypoxia‐inducible factor 1α and its downstream effector VEGFA, all of which are participants in inflammation. We concluded that signaling with lung preservation drives expression of inflammatory mediators that potentially predispose the donor lung to an inflammatory response after transplant.
The authors investigate the effect of halted blood flow or ischemia on donor lungs during storage and report that the mechanosignaling associated with loss of flow leads to the induction of several inflammatory mediators that may predispose the donor lung to inflammation‐induced oxidative damage posttransplant.