Receptor for Advanced Glycation End-Products Is a Marker of Type I Cell Injury in Acute Lung Injury

• Published in: American journal of respiratory and critical care medicine Vol. 173; no. 9; pp. 1008 - 1015
• Main Authors: Uchida, Tokujiro, Shirasawa, Madoka, Ware, Lorraine B, Kojima, Katsuo, Hata, Yutaka, Makita, Koshi, Mednick, Gabe, Matthay, Zachary A, Matthay, Michael A
• Format: Journal Article
• Language: English
• Published: New York, NY Am Thoracic Soc 01-05-2006; American Lung Association; American Thoracic Society
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Antibodies; Biological and medical sciences; Biomarkers; Blood. Blood and plasma substitutes. Blood products. Blood cells. Blood typing. Plasmapheresis. Apheresis; Bone marrow, stem cells transplantation. Graft versus host reaction; Bronchoalveolar Lavage Fluid - chemistry; C. Critical Care; Case-Control Studies; Committees; Edema; Humans; Hydrochloric Acid; Intensive care medicine; Lavage; Ligands; Lipopolysaccharides; Male; Medical sciences; Ostomy; Plasma; Proteins; Pulmonary Alveoli - metabolism; Pulmonary Edema - complications; Pulmonary Edema - metabolism; Rats; Rats, Sprague-Dawley; Receptor for Advanced Glycation End Products; Receptors, Immunologic - metabolism; Respiratory distress syndrome; Respiratory Distress Syndrome, Adult - complications; Respiratory Distress Syndrome, Adult - metabolism; Respiratory Mucosa - metabolism; Severity of Illness Index; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; United States > US; San Francisco California; California; pulmonary edema; Lung disease; Intensive care; Respiratory disease; Biological marker; Epithelium; Lung edema; Glycation; alveolar epithelium; acute respiratory distress syndrome; biological markers; Respiratory distress; Resuscitation
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200509-1477OC

Receptor for advanced glycation end-products (RAGE) is one of the alveolar type I cell-associated proteins in the lung.
To test the hypothesis that RAGE is a marker of alveolar epithelial type I cell injury.
Rats were instilled intratracheally with 10 mg/kg lipopolysaccharide or hydrochloric acid. RAGE levels were measured in the bronchoalveolar lavage (BAL) and serum in the rats and in the pulmonary edema fluid and plasma from patients with acute lung injury (ALI; n = 22) and hydrostatic pulmonary edema (n = 11).
In the rat lung injury studies, RAGE was released into the BAL and serum as a single soluble isoform sized approximately 48 kD. The elevated levels of RAGE in the BAL correlated well with the severity of experimentally induced lung injury. In the human studies, the RAGE level in the pulmonary edema fluid was significantly higher than the plasma level (p < 0.0001). The median edema fluid/plasma ratio of RAGE levels was 105 (interquartile range, 55-243). The RAGE levels in the pulmonary edema fluid from patients with ALI were higher than the levels from patients with hydrostatic pulmonary edema (p < 0.05), and the plasma RAGE level in patients with ALI were significantly higher than the healthy volunteers (p < 0.001) or patients with hydrostatic pulmonary edema (p < 0.05).
RAGE is a marker of type I alveolar epithelial cell injury based on experimental studies in rats and in patients with ALI.