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Intraportal lipopolysaccharide suppresses pulmonary antibacterial defense mechanisms
C M Mason1, E Dobard, W R Summer
1Pulmonary/Critical Care Medicine, Louisiana State University School of Medicine, New Orleans, USA.
Abstract:
Translocation of enteric bacteria or their components (or both) has been postulated to play a role in precipitating sepsis or the systemic inflammatory response syndrome. To simulate the effects of translocation on pulmonary host defenses, lipopolysaccharide was injected into the portal vein of normal rats that were subsequently challenged by aerosol inoculation with Pseudomonas aeruginosa. Injection of LPS into the portal vein resulted in increased serum tumor necrosis factor (TNF)-alpha levels and reduction in lung clearance of P. aeruginosa after aerosol challenge. There were corresponding reductions in alveolar neutrophil recruitment, diminished alveolar macrophage phagocytosis and superoxide anion (O2-) production, and diminished lung TNF recovered by bronchoalveolar lavage. Furthermore, prior intravenous injection of recombinant TNF-alpha reproduced the defective bacterial clearance, the altered recruitment of airspace neutrophils, and the defective alveolar macrophage phagocytosis. Thus, systemic TNF-alpha is important in altering pulmonary defenses, and this work supports the concept that bacterial translocation may adversely affect host defenses in distant organs.
Insights
Bacterial translocation may impair lung defenses by increasing systemic tumor necrosis factor-alpha (TNF-alpha). This study shows TNF-alpha disrupts pulmonary immune responses, affecting bacterial clearance and macrophage function.
Area of Science:
- Immunology
- Pulmonary Medicine
- Microbiology
Background:
- Bacterial translocation is a proposed mechanism contributing to sepsis and systemic inflammatory response syndrome.
- Understanding how translocation impacts distant organ defenses is crucial for managing inflammatory conditions.
Purpose of the Study:
- To investigate the effects of simulated bacterial translocation on pulmonary host defenses in rats.
- To elucidate the role of tumor necrosis factor-alpha (TNF-alpha) in mediating these effects.
Main Methods:
- Rats received portal vein injections of lipopolysaccharide (LPS) to mimic translocation.
- Pulmonary challenge with Pseudomonas aeruginosa via aerosol inoculation.
- Assessed serum TNF-alpha, bacterial clearance, neutrophil recruitment, and alveolar macrophage function.
Main Results:
- Portal vein LPS increased serum TNF-alpha and impaired lung clearance of P. aeruginosa.
- Reduced alveolar neutrophil recruitment and diminished macrophage phagocytosis and superoxide production were observed.
- Intravenous TNF-alpha administration replicated these pulmonary defense deficits.
Conclusions:
- Systemic TNF-alpha plays a significant role in compromising pulmonary immune defenses.
- These findings support the hypothesis that bacterial translocation can adversely affect host defenses in remote organs like the lungs.