title: How to measure alterations in alveolar barrier function as a marker of lung injury.
abstract: The alveolar capillary membrane maintains the proper water and solute content of the epithelial lining fluid at the alveolar air-liquid interface, which is critical for adequate gas exchange in the lung. This is possible due to the alveolar fluid clearance (AFC) capacity of this membrane that assists in the removal of salt and water from the alveolar air spaces. The alveolar capillary membrane also provides a barrier that restricts the passage of proteins and water from the interstitial and vascular compartments into the alveolar air spaces. This restricted passage is due to the presence of tight junctions between adjacent alveolar epithelial cells. Severe injury to the alveolar epithelial/endothelial membrane results in increased protein permeability and impairment of AFC, which leads to the formation of protein-rich edema with the consequent deterioration of gas exchange. Many animal models of lung injury, focused on damage of the alveolar-capillary membrane, assess the AFC capacity and the barrier function. We describe a simple method to assess the AFC rate in normal and pathological conditions in mice. We also describe two complementary methods to assess the alveolar-capillary barrier function, which require measuring the concentration of endogenous plasma proteins in bronchoalveolar lavage fluid and detection of tight-junction proteins in lung tissue by immunofluorescence.
authors: Hospital Universitario de Getafe, Servicio de Cuidados Intensivos, CIBER de Enfermedades Respiratorias, Getafe, Madrid, Spain.
authors: Raquel
authors: R
authors: Herrero
authors: Medical Research Service of the Veterans Affairs Puget Sound Health Care Center and Center for Lung Biology, Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Washington, Seattle, Washington.
authors: Gustavo
authors: G
authors: Matute-Bello
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism*; D015824:Blood-Air Barrier / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002199:Capillary Permeability; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D055370:Lung Injury / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D011650:Pulmonary Alveoli / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D062725:Tight Junction Proteins / Q000378:metabolism*; D057188:Workflow
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D062725:Tight Junction Proteins
keywords: alveolar fluid clearance; barrier function; lung injury; mice; protein permeability; tight-junction proteins
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