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TRANSLATIONAL PHYSIOLOGY
Acute Lung Injury
1Department of Medicine, School of Medicine, Keio University, Tokyo, 160-8582; 2Department of Anesthesiology, Kyoto Prefectural University of Medicine, Kyoto, 602-8566; 4Department of Molecular and Internal Medicine, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, 734-8551; 5Department of Anesthesiology, School of Medicine, Keio University, Tokyo, 160-8582, Japan; 3Departments of Pediatrics and Medicine, School of Medicine, University of Utah, Salt Lake City, Utah 84132; and 6Medicine, Primary and Specialty Medicine Service Line, Veterans Affairs/Puget Sound Medical Center, Seattle, Washington 98108; and 7Medicine and Anesthesia, Cardiovascular Research Institute, University of California at San Francisco, San Francisco, California 94143
Submitted 9 December 2002 ; accepted in final form 26 August 2003
KL-6 is a pulmonary epithelial mucin more prominently expressed on the surface membrane of alveolar type II cells when these cells are proliferating, stimulated, and/or injured. We hypothesized that high levels of KL-6 in epithelial lining fluid and plasma would reflect the severity of lung injury in patients with acute lung injury (ALI). Epithelial lining fluid was obtained at onset (day 0) and day 1 of acute respiratory distress syndrome (ARDS)/ALI by bronchoscopic microsampling procedure in 35 patients. On day 0, KL-6 and albumin concentrations in epithelial lining fluid were significantly higher than in normal controls (P < 0.001), and the concentrations of KL-6 in epithelial lining fluid (P < 0.002) and in plasma (P < 0.0001) were higher in nonsurvivors than in survivors of ALI/ARDS. These observations were corroborated by the immunohistochemical localization of KL-6 protein expression in the lungs of nonsurvivors with ALI and KL-6 secretion from cultured human alveolar type II cells stimulated by proinflammatory cytokines. Because injury to distal lung epithelial cells, including alveolar type II cells, is important in the pathogenesis of ALI, the elevation of KL-6 concentrations in plasma and epithelial lining fluid could be valuable indicators for poor prognosis in clinical ALI.
alveolar type II cell; pulmonary edema; microsampling
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