Elevation of KL-6, a lung epithelial cell marker, in plasma and epithelial lining fluid in acute respiratory distress syndrome.
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.
Ishizaka
Akitoshi
A
Department of Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 Japan. ishizaka@cpnet.med.keio.ac.jp
Matsuda
Tomoyuki
T
Albertine
Kurt H
KH
Koh
Hidefumi
H
Tasaka
Sadatomo
S
Hasegawa
Naoki
N
Kohno
Nobuoki
N
Kotani
Toru
T
Morisaki
Hiroshi
H
Takeda
Junzo
J
Nakamura
Morio
M
Fang
Xiaohui
X
Martin
Thomas R
TR
Matthay
Michael A
MA
Hashimoto
Satoru
S
D000328:Adult; D000368:Aged; D000941:Antigens / Q000097:blood*; D000951:Antigens, Neoplasm; D015415:Biomarkers; D001992:Bronchoalveolar Lavage Fluid; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D006023:Glycoproteins / Q000097:blood* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D018396:Mucin-1; D009077:Mucins; D011650:Pulmonary Alveoli / Q000378:metabolism / Q000473:pathology; D011654:Pulmonary Edema / Q000378:metabolism* / Q000473:pathology*; D012128:Respiratory Distress Syndrome / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D020545:Respiratory Mucosa / Q000378:metabolism / Q000473:pathology; D015996:Survival Rate
D000941:Antigens; D000951:Antigens, Neoplasm; D015415:Biomarkers; D006023:Glycoproteins; C060192:MUC1 protein, human; D018396:Mucin-1; D009077:Mucins