Hypoxia aggravates lipopolysaccharide‐induced lung injury

• Published in: Clinical and experimental immunology Vol. 141; no. 2; pp. 248 - 260
• Main Authors: Vuichard, D., Ganter, M. T., Schimmer, R. C., Suter, D., Booy, C., Reyes, L., Pasch, T., Beck‐Schimmer, B.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.08.2005; Blackwell; Oxford University Press; Blackwell Science Inc
• Subjects: acute lung injury; acute respiratory distress syndrome; Animals; Basic Immunology; Biological and medical sciences; Bronchoalveolar Lavage Fluid - immunology; Capillary Permeability - immunology; Chemokine CCL4; Disease Models, Animal; endotoxin; Enzyme-Linked Immunosorbent Assay - methods; Fundamental and applied biological sciences. Psychology; Fundamental immunology; hypoxia; Hypoxia - complications; Hypoxia - immunology; Immunopathology; Inflammation Mediators - metabolism; Lipopolysaccharides - toxicity; lung inflammation; Macrophage Inflammatory Proteins - metabolism; Macrophages, Alveolar - immunology; Male; Medical sciences; Neutrophil Infiltration - immunology; Peroxidase - metabolism; Pulmonary Surfactant-Associated Protein B - metabolism; Rats; Rats, Wistar; Respiratory Distress Syndrome, Adult - etiology; Respiratory Distress Syndrome, Adult - immunology; Respiratory Distress Syndrome, Adult - metabolism; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - genetics; Tumor Necrosis Factor-alpha - metabolism; Immunopathology; Lung disease; Oxygen; Respiratory disease; Acute; Inflammation; Endotoxin; acute lung injury; Toxin; Immunology; Lipopolysaccharide; acute respiratory distress syndrome; Respiratory distress; Hypoxia; lung inflammation
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.2005.02835.x

Summary The animal model of inflammatory response induced by intratracheal application of lipopolysaccharide includes many typical features of acute lung injury or the acute respiratory distress syndrome. A number of experimental investigations have been performed to characterize the nature of this injury more effectively. In inflammatory conditions, hypoxia occurs frequently before and in parallel with pulmonary and non‐pulmonary pathological events. This current study was designed to examine the in vivo effect of hypoxia as a potentially aggravating condition in endotoxin‐induced lung injury. Lipopolysaccharide, 150 µg, was instilled intratracheally into rat lungs, and thereafter animals were exposed to either normoxia or hypoxia (10% oxygen). Lungs were collected 2, 4, 6 and 8 h later. Inflammatory response and tissue damage were evaluated by quantitative analysis of inflammatory cells and mediators, surfactant protein and vascular permeability. A significantly enhanced neutrophil recruitment was seen in lipopolysaccharide‐animals exposed to hypoxia compared to lipopolysaccharide‐animals under normoxia. This increased neutrophil accumulation was triggered by inflammatory mediators such as tumour necrosis factor‐α and macrophage inflammatory protein‐1β, secreted by alveolar macrophages. Determination of vascular permeability and surfactant protein‐B showed enhanced concentrations in lipopolysaccharide‐lungs exposed to hypoxia, which was absent in animals previously alveolar macrophage‐depleted. This study demonstrates that hypoxia aggravates lipopolysaccharide injury and therefore represents a second hit injury. The additional hypoxia‐induced inflammatory reaction seems to be predominantly localized in the respiratory compartment, underlining the compartmentalized nature of the inflammatory response.