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Volume 3 Supplement 1


  • Poster presentation
  • Open Access

Inhibition of receptor for advanced glycation end-products (RAGE) improves alveolar fluid clearance and lung injury in a mouse model of acute respiratory distress syndrome (ARDS)

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Intensive Care Medicine Experimental20153 (Suppl 1) :A804

  • Published:


  • Lung Injury
  • Sham Group
  • Acute Respiratory Distress Syndrome
  • Alveolar Type
  • Decoy Receptor


The receptor for advanced glycation end-products (RAGE) is a transmembrane multipattern receptor abundantly expressed on the basal surface of alveolar type (AT) I cells. RAGE is implicated in ARDS-associated alveolar inflammation [1,2], but its precise roles in lung injury remain unknown. It has been shown recently that RAGE axis could impact alveolar fluid clearance (AFC) through the modulation of epithelial sodium channels [3]. In mouse models of sepsis and of ARDS, treatment with anti-RAGE monoclonal antibody decreased mortality, and treatment with recombinant soluble RAGE (sRAGE, acting as a decoy receptor) was associated with improved lung injury.


Using a murine model of ARDS, we evaluated whether RAGE modulation could regulate lung injury and AFC.


60 anesthetised male C57BL/6JTj mice were divided in 4 groups; 3 of them underwent orotracheal installation of hydrochloric acid (day 0). Among these acid-injured mice, some were intravenously treated with an anti-RAGE monoclonal antibody (mAb) or intraperitoneal recombinant soluble RAGE (sRAGE). Mice from the Sham group underwent orotracheal instillation of saline and served as controls. At specified time-points (day 0, 1, 2 and 4), lung injury was assessed after a 30-minute period of mechanical ventilation by analysis of blood gases, alvolar permeability index, bronchoalveolar lavage (BAL) fluid content in interleukin (IL)-6 and AFC. AFC was calculated detecting changes into alveolar protein levels over time.


Acid-injured mice had higher permeability indexes, higher BAL IL-6 and marked hypoxemia on day 1 and 2, as compared with sham animals. AFC rates and PaO2/FiO2 ratios were higher in controls (35%/30min and 281 [262-319], respectively) than in HCl-injured mice on day 1 (8% and 181 [176-198], respectively, P < 0.0001) and day 2 (9% and 186 [174-205], respectively, P < 0.0001).

RAGE inhibition restored AFC on day 1 in both mAb-treated (8% versus 36%, p = 0.009) and sRAGE-treated (8% versus 37% p = 0,009) mice. RAGE inhibition significantly improved both PaO2/FiO2 ratio and permeability index on day 1, day 2, and anti-RAGE therapy could prevent increased BAL IL-6 levels on day 1 an day 2 in HCl-treated mice.


Our results support the efficacy of a RAGE inhibition strategy in improving AFC and lung injury in a translational mouse model of ARDS, and RAGE pathway may represent a therapeutic target during ARDS. Such findings should stimulate further research on the mechanistic links between RAGE pathway, AFC and lung alveolar injury and its resolution.
Figure 1
Figure 1

Mice lung injury over time.

Authors’ Affiliations

CHU Clermont-Ferrand, Department of Anaesthesiology and Intensive Care Medicine, Clermont-Ferrand, France
Auvergne University, R2D2 - EA7281, Clermont-Ferrand, France
CHU Clermont-Ferrand, Department of Medical Biochemistry and Molecular Biology, Clermont-Ferrand, France


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  2. Crit Care Med. 2011, 39 (3): 480-488. 10.1097/CCM.0b013e318206b3ca.Google Scholar
  3. Am J Respir Cell Mol Biol. 2015, 52 (1): 75-87. 10.1165/rcmb.2014-0002OC. JanGoogle Scholar


© Blondonnet et al.; 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.