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Depletion of phagocytes in the reticuloendothelial system causes increased inflammation and mortality in rabbits withPseudomonas aeruginosapneumonia
- Source :
- American Journal of Physiology-Lung Cellular and Molecular Physiology. 296:L198-L209
- Publication Year :
- 2009
- Publisher :
- American Physiological Society, 2009.
-
Abstract
- Phagocytes of the reticuloendothelial system are important in clearing systemic infection; however, the role of the reticuloendothelial system in the response to localized infection is not well-documented. The major goals of this study were to investigate the roles of phagocytes in the reticuloendothelial system in terms of bacterial clearance and inflammatory modulation in sepsis caused by Pseudomonas pneumonia. Macrophages in liver and spleen were depleted by administering liposome encapsulated dichloromethylene diphosphonate (clodronate) intravenously 36 h before the instillation of Pseudomonas aeruginosa into the lungs of anesthetized rabbits. Blood samples were analyzed for bacteria and cytokine concentrations. Lung injury was assessed by the bidirectional flux of albumin and by wet-to-dry weight ratios. Blood pressure and cardiac outputs decreased more rapidly and bacteremia occurred earlier in the clodronate-treated rabbits compared with the nondepleted rabbits. Plasma TNF-α (1.08 ± 0.54 vs. 0.08 ± 0.02 ng/ml) and IL-8 (6.8 ± 1.5 vs. 0.0 ± 0.0 ng/ml) were higher in the depleted rabbits. The concentration of IL-10 in liver of the macrophage-depleted rabbits was significantly lower than in normal rabbits at 5 h. Treatment of macrophage-depleted rabbits with intravenous IL-10 reduced plasma proinflammatory cytokine concentrations and reduced the decline in blood pressure and cardiac output. These results show that macrophages in the reticuloendothelial system have critical roles in controlling systemic bacteremia and reducing systemic inflammation, thereby limiting the systemic effects of a severe pulmonary bacterial infection.
- Subjects :
- Male
Pulmonary and Respiratory Medicine
Physiology
Bacteremia
Blood Pressure
Enzyme-Linked Immunosorbent Assay
Inflammation
Spleen
Biology
Lung injury
Systemic inflammation
Proinflammatory cytokine
Sepsis
Physiology (medical)
Pneumonia, Bacterial
medicine
Animals
Pseudomonas Infections
Mononuclear Phagocyte System
Phagocytes
Macrophages
Articles
Lung Injury
Cell Biology
Mononuclear phagocyte system
medicine.disease
Survival Rate
medicine.anatomical_structure
Liver
Liposomes
Pseudomonas aeruginosa
Immunology
Cytokines
Tumor necrosis factor alpha
Rabbits
Clodronic Acid
medicine.symptom
Subjects
Details
- ISSN :
- 15221504 and 10400605
- Volume :
- 296
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Lung Cellular and Molecular Physiology
- Accession number :
- edsair.doi.dedup.....fc0cfe27085708943b6b168cbd54594a