Blockade of receptor for advanced glycation end product attenuates pulmonary reperfusion injury in mice

David I. Sternberg, Ram Gowda, Divya Mehra, Wu Qu, Alan Weinberg, William Twaddell, Joydeep Sarkar, Allison Wallace, Barry Hudson, Frank D'Ovidio, Selim Arcasoy, Ravichandran Ramasamy, Jeanine D'Armiento, Ann Marie Schmidt, Joshua R. Sonett

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


Objective: The receptor for advanced glycation end products (RAGE) is expressed at high levels in the lung, particularly in type 1 alveolar cells, and has been shown to amplify injury triggered by acute stress. Previous studies suggest serum concentrations of soluble RAGE increase during pulmonary reperfusion injury after transplantation. RAGE blockade has been shown to suppress hepatic and cardiac ischemia and reperfusion injury in mice. Thus we tested the hypothesis that RAGE mediates tissue-injury mechanisms in ischemia and reperfusion injury in the lung. Methods: C57BL/6 mice were subjected to 30 minutes of pulmonary ischemia by clamping the left hilum, followed by 60 minutes of reperfusion. Lung function was assessed by means of blood gas analysis, and capillary leak was assessed by injecting fluorescein isothiocyanate-labeled albumin and comparing fluorescence in bronchial lavage fluid with that in serum. Histologic analysis of the lung was performed by a pathologist naive to the experimental conditions. Results: In animals subjected to RAGE blockade, significant increases in Po2 (108 vs 73 mm Hg, P = .0094) and more than 3-fold decrease in capillary leak Relative Fluorescent Units (RFU, 6.12 vs 1.75; P = .001) were observed. Histologic examination revealed significant injury reduction in soluble RAGE-treated animals versus control animals. RAGE knockout mice exhibited a protected phenotype when exposed to pulmonary ischemia and reperfusion. Additionally, interleukin 8 production and nuclear factor κB activation were increased in control mice. Conclusion: Abrogation of RAGE signaling attenuates pulmonary ischemia and reperfusion injury. This study suggests that RAGE might play a central role in pulmonary reperfusion injury and in transplantation and that blockade of RAGE might offer a potential target to abrogate pulmonary reperfusion injury in clinical transplantation.

Original languageEnglish (US)
Pages (from-to)1576-1585
Number of pages10
JournalJournal of Thoracic and Cardiovascular Surgery
Issue number6
StatePublished - Dec 2008
Externally publishedYes

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine


Dive into the research topics of 'Blockade of receptor for advanced glycation end product attenuates pulmonary reperfusion injury in mice'. Together they form a unique fingerprint.

Cite this