The receptor for advanced glycation end products mediates lung endothelial activation by RBCs

Area of Science:

• Immunology
• Vascular Biology
• Pulmonary Medicine

Background:

• The receptor for advanced glycation end products (RAGE) is a key mediator in various diseases.
• RAGE expression is known on systemic endothelium, but its role in lung endothelium is uncharacterized.
• RAGE ligands can induce RAGE expression, and stored red blood cells carry RAGE ligands.

Purpose of the Study:

• To investigate the expression and function of RAGE on lung endothelium.
• To determine if red blood cell (RBC) transfusion augments RAGE expression on lung endothelium.
• To elucidate the role of RAGE in RBC transfusion-induced lung inflammation and endothelial activation.

Main Methods:

• Utilized in vitro human cell models and in vivo mouse models.
• Established RAGE presence on lung endothelium.
• Investigated the effects of syngeneic RBC transfusion on RAGE expression and lung inflammation in wild-type and RAGE knockout mice.

Main Results:

• Confirmed RAGE expression on lung endothelium.
• RBC transfusion significantly increased lung endothelial RAGE expression.
• Transfusion led to enhanced lung inflammation and endothelial activation, evidenced by increased high mobility group box 1 and vascular cell adhesion molecule 1 expression.
• These transfusion-induced effects were absent in RAGE knockout mice, confirming RAGE mediation.

Conclusions:

• RAGE is inducibly expressed on lung endothelium.
• RBC transfusion triggers increased RAGE expression and subsequent endothelial activation in the lungs.
• RAGE plays a critical role in the inflammatory response following RBC transfusion in the lungs.