Inducible nitric oxide synthase and heme oxygenase-1 in the lung during lipopolysaccharide tolerance and cross tolerance
| Autor: | Rene Schmidt, Paula A. Zacharowski, Jörg Weimann, Reinhard Berkels, Alexander Koch, Kai Zacharowski, Olaf Boehm, Hauke Rensing, Stephan A. Loer, Sonja Reingruber, Simon J. Foster |
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| Rok vydání: | 2007 |
| Předmět: |
Lipopolysaccharides
Male Lipopolysaccharide Nitric Oxide Synthase Type II Pharmacology Critical Care and Intensive Care Medicine chemistry.chemical_compound Intensive care Gene expression Immune Tolerance medicine Animals Rats Wistar Lung Gram-Positive Bacterial Infections chemistry.chemical_classification biology Pulmonary edema medicine.disease Shock Septic Rats Cross-tolerance Nitric oxide synthase Heme oxygenase Enzyme Gene Expression Regulation chemistry Biochemistry Desensitization Immunologic biology.protein Gram-Negative Bacterial Infections Heme Oxygenase-1 |
| Zdroj: | Critical Care Medicine. 35:2775-2784 |
| ISSN: | 0090-3493 |
| Popis: | Pretreatment with low-dose lipopolysaccharide protects cells/organs against a subsequent lethal Gram-negative (lipopolysaccharide tolerance) or Gram-positive (cross tolerance) stimulus. We determined whether this occurs in the rat lung. The involvement of inducible nitric oxide synthase and heme oxygenase-1 was evaluated.Laboratory study.University hospital laboratory.Anesthetized male Wistar rats.To test the hypothesis, rats received saline or lipopolysaccharide (1 mg/kg). At 2, 4, 8, 16, or 24 hrs later, blood samples and lung tissue were taken to determine messenger RNA, protein concentration, and activity of inducible nitric oxide synthase and heme oxygenase-1. In additional experiments, rats were challenged with lipopolysaccharide (1 mg/kg) and subjected to Gram-negative (lipopolysaccharide) or Gram-positive (lipoteichoic acid and peptidoglycan) shock 24 hrs later. These studies were carried out in the presence and absence of inducible nitric oxide synthase or heme oxygenase-1 inhibitors (1400W or tin protoporphyrin IX). Following 6 hrs of shock, lung tissue was taken to determine lung damage and heme oxygenase-1 concentration and activity.In the rat lung, lipopolysaccharide (1 mg/kg) induced a significant increase in inducible nitric oxide synthase protein at 8 hrs with a corresponding increase in plasma nitrate/nitrite at 8-16 hrs. Simultaneously, heme oxygenase-1 messenger RNA transcripts were observed at 8-16 hrs, and maximal expression of the protein followed (24 hrs). Pretreatment with low-dose lipopolysaccharide reduced myeloperoxidase activity (neutrophil infiltration) and wet-dry ratio (pulmonary edema) in the lungs of animals subjected to Gram-negative or Gram-positive shock, demonstrating tolerance. Pretreatment with low-dose lipopolysaccharide and the selective inducible nitric oxide synthase inhibitor 1400W reduced heme oxygenase-1 protein expression, and lung protection was abolished. Tin protoporphyrin IX did not affect heme oxygenase-1 expression, but heme oxygenase activity and lung protection were significantly reduced.We propose that nitric oxide (most likely inducible nitric oxide synthase derived) regulates the induction of heme oxygenase-1 in the lung, which in turn plays an important part in pulmonary protection during lipopolysaccharide tolerance and cross tolerance. |
| Databáze: | OpenAIRE |
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