Depletion of phagocytes in the reticuloendothelial system causes increased inflammation and mortality in rabbits withPseudomonas aeruginosapneumonia
| Autor: | Teiji Sawa, Maria Ota, Thomas R. Martin, Jeanine P. Wiener-Kronish, Osamu Kajikawa, Keelung Hong, Kiyoyasu Kurahashi |
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| Rok vydání: | 2009 |
| Předmět: |
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 |
| Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 296:L198-L209 |
| ISSN: | 1522-1504 1040-0605 |
| DOI: | 10.1152/ajplung.90472.2008 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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