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Updated: Feb 25, 2026
A Model of Self-limited Acute Lung Injury by Unilateral Intra-bronchial Acid Instillation
Published on: August 30, 2019
RAGE inhibition reduces acute lung injury in mice
Raiko Blondonnet1,2, Jules Audard3,4, Corinne Belville4
1Department of Perioperative Medicine, CHU Clermont-Ferrand, Clermont-Ferrand, France. rblondonnet@chu-clermontferrand.fr.
Abstract:
The receptor for advanced glycation end-products (RAGE) is involved in inflammatory response during acute respiratory distress syndrome (ARDS). Growing body of evidence support strategies of RAGE inhibition in experimental lung injury, but its modalities and effects remain underinvestigated. Anesthetised C57BL/6JRj mice were divided in four groups; three of them underwent orotracheal instillation of acid and were treated with anti-RAGE monoclonal antibody (mAb) or recombinant soluble RAGE (sRAGE), acting as a decoy receptor. The fourth group served as a control. Lung injury was assessed by the analysis of blood gases, alveolar permeability, histology, AFC, and cytokines. Lung expression and distribution epithelial channels ENaC, Na,K-ATPase, and aquaporin (AQP)-5 were assessed. Treatment with either anti-RAGE mAb or sRAGE improved lung injury, arterial oxygenation and decreased alveolar inflammation in acid-injured animals. Anti-RAGE therapies were associated with restored AFC and increased lung expression of AQP-5 in alveolar cell. Blocking RAGE had potential therapeutic effects in a translational mouse model of ARDS, possibly through a decrease in alveolar type 1 epithelial cell injury as shown by restored AFC and lung AQP-5 expression. Further mechanistic studies are warranted to describe intracellular pathways that may control such effects of RAGE on lung epithelial injury and repair.
Insights
Blocking the receptor for advanced glycation end-products (RAGE) with antibodies or decoy receptors improved lung injury and oxygenation in a mouse model of acute respiratory distress syndrome (ARDS). These therapies may protect alveolar epithelial cells.
Area of Science:
- Pulmonary Medicine
- Immunology
- Cell Biology
Background:
- The receptor for advanced glycation end-products (RAGE) plays a role in the inflammatory response during acute respiratory distress syndrome (ARDS).
- Strategies targeting RAGE inhibition show promise for experimental lung injury, but their specific effects require further investigation.
- Understanding RAGE's role in lung injury is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the therapeutic potential of blocking RAGE in a translational mouse model of ARDS.
- To assess the effects of anti-RAGE monoclonal antibody (mAb) and recombinant soluble RAGE (sRAGE) on lung injury parameters.
- To examine the impact of RAGE inhibition on epithelial ion channels and water transport in the lungs.
Main Methods:
- C57BL/6JRj mice were subjected to acid-induced lung injury and treated with anti-RAGE mAb or sRAGE.
- Lung injury was evaluated using blood gas analysis, alveolar permeability measurements, histology, and cytokine profiling.
- Expression and distribution of epithelial sodium channels (ENaC), Na,K-ATPase, and aquaporin-5 (AQP-5) were assessed in lung tissue.
Main Results:
- Both anti-RAGE mAb and sRAGE treatments significantly improved lung injury and arterial oxygenation in acid-injured mice.
- RAGE inhibition reduced alveolar inflammation and restored alveolar fluid clearance (AFC).
- Therapies increased lung AQP-5 expression in alveolar cells, suggesting protection of alveolar type 1 cells.
Conclusions:
- Blocking RAGE demonstrates therapeutic potential in a mouse model of ARDS.
- RAGE inhibition may protect alveolar type 1 epithelial cells, evidenced by restored AFC and increased AQP-5 expression.
- Further research is needed to elucidate the intracellular mechanisms underlying RAGE's effects on lung epithelial injury and repair.
