Receptor for advanced glycation end-products is a marker of type I cell injury in acute lung injury.
BACKGROUND
Receptor for advanced glycation end-products (RAGE) is one of the alveolar type I cell-associated proteins in the lung.


OBJECTIVE
To test the hypothesis that RAGE is a marker of alveolar epithelial type I cell injury.


METHODS
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).


RESULTS
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).


CONCLUSIONS
RAGE is a marker of type I alveolar epithelial cell injury based on experimental studies in rats and in patients with ALI.
Uchida
Tokujiro
T
Department of Anesthesiology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. uchida.mane@tmd.ac.jp
Shirasawa
Madoka
M
Ware
Lorraine B
LB
Kojima
Katsuo
K
Hata
Yutaka
Y
Makita
Koshi
K
Mednick
Gabe
G
Matthay
Zachary A
ZA
Matthay
Michael A
MA
D000818:Animals; D015415:Biomarkers; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016022:Case-Control Studies; D006801:Humans; D006851:Hydrochloric Acid; D008070:Lipopolysaccharides; D008297:Male; D011650:Pulmonary Alveoli / Q000378:metabolism*; D011654:Pulmonary Edema / Q000150:complications / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D012128:Respiratory Distress Syndrome / Q000150:complications / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000378:metabolism; D012720:Severity of Illness Index
D015415:Biomarkers; D008070:Lipopolysaccharides; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D006851:Hydrochloric Acid