Hypoxia aggravates lipopolysaccharide-induced lung injury.
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 microg, 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-alpha and macrophage inflammatory protein-1beta, 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.
Vuichard
D
D
Institute of Physiology, University of Zurich, CH-8057 Zurich, Switzerland.
Ganter
M T
MT
Schimmer
R C
RC
Suter
D
D
Booy
C
C
Reyes
L
L
Pasch
T
T
Beck-Schimmer
B
B
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002199:Capillary Permeability / Q000276:immunology; D054407:Chemokine CCL4; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D000860:Hypoxia / Q000150:complications* / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000276:immunology; D008297:Male; D020556:Neutrophil Infiltration / Q000276:immunology; D009195:Peroxidase / Q000378:metabolism; D037701:Pulmonary Surfactant-Associated Protein B / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D012128:Respiratory Distress Syndrome / Q000209:etiology* / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D054407:Chemokine CCL4; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; D037701:Pulmonary Surfactant-Associated Protein B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase