Rationale: Receptor for advanced glycation end-products (RAGE) is one of the alveolar type I cell-associated proteins in the lung. Objectives: 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 ϭ 22) and hydrostatic pulmonary edema (n ϭ 11). Main Results: In the rat lung injury studies, RAGE was released into the BAL and serum as a single soluble isoform sized ‫ف‬ 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 Ͻ 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 Ͻ 0.05), and the plasma RAGE level in patients with ALI were significantly higher than the healthy volunteers (p Ͻ 0.001) or patients with hydrostatic pulmonary edema (p Ͻ 0.05). Conclusion: RAGE is a marker of type I alveolar epithelial cell injury based on experimental studies in rats and in patients with ALI.Keywords: acute respiratory distress syndrome; alveolar epithelium; biological markers; pulmonary edemaReceptor for advanced glycation end-products (RAGE) is one of the alveolar type I cell-associated proteins in the lung (1, 2). Although it is also expressed in endothelial cells in large vessels (3, 4) and nervous tissues (5, 6), the transcript of RAGE is most prominent in the lung (3) and apparently not expressed in lung microvascular endothelia (7,8). Immunoelectron microscopy of RAGE demonstrated that its expression is localized to the basal membrane of alveolar type I epithelial cells (7,8 binding site and two C-type immunogloblin-like regions), a transmembrane domain, and a cytosolic tail, that are essential for post-RAGE signaling (9). In general, RAGE is a multiligandbinding receptor that can bind advanced glycation end products, amyloid ␤-peptide, S100 proteins, and high-mobility group box-1 (10-12). RAGE-ligand interaction results in intracellular signaling, which leads to activation of the proinflammatory transcription factor nuclear factor-B (NF-B). This cellular activation is related to inflammatory processes or tissue injury, such as diabetic microvascular injury, amyloidosis, and immune-inflammatory process (10-12). RAGE knockout mice were recently reported to be resistant to septic shock induced by cecal ligation and puncture (13), suggesting that RAGE potentially plays a role in systemic acute inflammation. However, the biochemical characteristics of RAGE in the lung in response to acute lung injury (ALI) have not been determined.Alveolar type I epithe...

Our results indicate that ghrelin is not a direct cause of increased food intake and weight gain during treatment with olanzapine or risperidone, whereas ghrelin is associated with metabolic change in patients receiving these agents.