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.

[1]  N. Kohno [Sialylated carbohydrate antigen KL-6]. , 2004, Nihon rinsho. Japanese journal of clinical medicine.

[2]  V. H. Lee,et al.  Monolayers of Human Alveolar Epithelial Cells in Primary Culture for Pulmonary Absorption and Transport Studies , 1999, Pharmaceutical Research.

[3]  G. Zimmerman,et al.  Fas and fas ligand are up-regulated in pulmonary edema fluid and lung tissue of patients with acute lung injury and the acute respiratory distress syndrome. , 2002, The American journal of pathology.

[4]  M. Matthay,et al.  Assessment of lungs rejected for transplantation and implications for donor selection , 2002, The Lancet.

[5]  A. Bersten,et al.  Elevated plasma surfactant protein-B predicts development of acute respiratory distress syndrome in patients with acute respiratory failure. , 2001, American journal of respiratory and critical care medicine.

[6]  David G. Morris,et al.  Reactive Nitrogen Species Inhibit Alveolar Epithelial Fluid Transport After Hemorrhagic Shock in Rats1 , 2001, The Journal of Immunology.

[7]  J. Takeda,et al.  New bronchoscopic microsample probe to measure the biochemical constituents in epithelial lining fluid of patients with acute respiratory distress syndrome , 2001, Critical care medicine.

[8]  M. Matthay,et al.  The acute respiratory distress syndrome. , 1996, The New England journal of medicine.

[9]  J. Whitsett,et al.  Serial changes in surfactant-associated proteins in lung and serum before and after onset of ARDS. , 1999, American journal of respiratory and critical care medicine.

[10]  J. Pittet,et al.  Acid-induced lung injury. Protective effect of anti-interleukin-8 pretreatment on alveolar epithelial barrier function in rabbits. , 1999, American journal of respiratory and critical care medicine.

[11]  T. Martin,et al.  Pathogenesis of septic shock in Pseudomonas aeruginosa pneumonia. , 1999, The Journal of clinical investigation.

[12]  M. Matthay,et al.  The alveolar space is the site of intense inflammatory and profibrotic reactions in the early phase of acute respiratory distress syndrome. , 1999, Critical care medicine.

[13]  N. Kohno,et al.  KL-6, a human MUC1 mucin, is chemotactic for human fibroblasts. , 1997, American journal of respiratory cell and molecular biology.

[14]  G. Zimmerman,et al.  Human endothelial cells synthesize ENA-78: relationship to IL-8 and to signaling of PMN adhesion. , 1997, American journal of respiratory cell and molecular biology.

[15]  J. Pittet,et al.  Biological markers of acute lung injury: prognostic and pathogenetic significance. , 1997, American journal of respiratory and critical care medicine.

[16]  M. Matthay,et al.  Early detection of type III procollagen peptide in acute lung injury. Pathogenetic and prognostic significance. , 1997, American journal of respiratory and critical care medicine.

[17]  K. Steinberg,et al.  Type III Procollagen Peptide in the Adult Respiratory Distress Syndrome: Association of Increased Peptide Levels in Bronchoalveolar Lavage Fluid with Increased Risk for Death , 1995, Annals of Internal Medicine.

[18]  M. Lamy,et al.  The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. , 1994, American journal of respiratory and critical care medicine.

[19]  J. Kirby,et al.  Constitutive expression of MHC and adhesion molecules by alveolar epithelial cells (type II pneumocytes) isolated from human lung and comparison with immunocytochemical findings. , 1994, Journal of cell science.

[20]  W. Gilks,et al.  Third international workshop on lung tumor and differentiation antigens: Overview of the results of the central data analysis , 1994, International journal of cancer. Supplement = Journal international du cancer. Supplement.

[21]  N. Kohno,et al.  KL-6, a mucin-like glycoprotein, in bronchoalveolar lavage fluid from patients with interstitial lung disease. , 1993, The American review of respiratory disease.

[22]  K. Steinberg,et al.  Safety of bronchoalveolar lavage in patients with adult respiratory distress syndrome. , 1993, The American review of respiratory disease.

[23]  M. Ligtenberg,et al.  Cell membrane-associated mucins and their adhesion-modulating property. , 1992, Trends in biochemical sciences.

[24]  W. Knaus,et al.  Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. , 1992, Chest.

[25]  M. Matthay,et al.  Differential responses of the endothelial and epithelial barriers of the lung in sheep to Escherichia coli endotoxin. , 1991, The Journal of clinical investigation.

[26]  P. Rogol Intact epithelial barrier function is critical for resolution of alveolar edema in humans. , 1991, The American review of respiratory disease.

[27]  A. Guz,et al.  Type II pneumocytes in mixed cell culture of human lung: a light and electron microscopic study. , 1990, Environmental health perspectives.

[28]  J. Edelson,et al.  Effects of two extracellular matrices on morphologic and biochemical properties of human type II cells in vitro. , 1989, The American review of respiratory disease.

[29]  N. Kohno,et al.  New serum indicator of interstitial pneumonitis activity. Sialylated carbohydrate antigen KL-6. , 1989, Chest.

[30]  N. Kohno,et al.  Detection of soluble tumor-associated antigens in sera and effusions using novel monoclonal antibodies, KL-3 and KL-6, against lung adenocarcinoma. , 1988, Japanese journal of clinical oncology.

[31]  J F Murray,et al.  An expanded definition of the adult respiratory distress syndrome. , 1988, The American review of respiratory disease.

[32]  N. Staub Lung water and solute exchange , 1978 .

[33]  C. Milstein,et al.  Continuous cultures of fused cells secreting antibody of predefined specificity , 1975, Nature.