Depletion of phagocytes in the reticuloendothelial system causes increased inflammation and mortality in rabbits with Pseudomonas aeruginosa pneumonia
Depletion of phagocytes in the reticuloendothelial system causes increased inflammation and mortality in rabbits with Pseudomonas aeruginosa pneumonia
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DOI：
10.1152/ajplung.90472.2008
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发表时间：
2009-02-01
影响因子：
4.9
通讯作者：
Wiener-Kronish, Jeanine P.
中科院分区：
文献类型：
--
作者：
Kurahashi, Kiyoyasu;Sawa, Teiji;Wiener-Kronish, Jeanine P.
首页--期刊主要分类--期刊细介绍--期刊题录与文摘--期刊详细文摘内容网状内皮系统中吞噬细胞的耗尽会增加铜绿假单胞菌肺炎兔的炎症和死亡率。Am J Physiol肺细胞分子Physiol 296：L198-L209,2009。网状内皮系统的吞噬细胞在清除全身性感染中是重要的；然而，网状内皮系统在局部感染反应中的作用还没有很好的文献。本研究的主要目的是探讨吞噬细胞在肺炎假单胞菌引起的脓毒症中在细菌清除和炎症调节中的作用。在麻醉兔肺内注入铜绿假单胞菌前36h，静脉注射脂质体包裹的二氯亚甲基二磷酸(氯屈膦)，以清除肝和脾中的巨噬细胞。对血样进行细菌和细胞因子浓度分析。通过双向白蛋白流量和湿/干重量比评估肺损伤。与未耗竭的兔相比，服用氯屈膦酸盐的兔的血压和心输出量下降更快，菌血症发生得更早。耗竭兔血浆肿瘤坏死因子-α(1.08+/-0.54对0.08+/-0.02 ng/ml)和IL-8(6.8+/-1.5对0.0+/-0.0 ng/ml)较高。静脉注射IL-10可降低血浆促炎细胞因子浓度，降低血压和心输出量的下降幅度。这些结果表明，网状内皮系统中的巨噬细胞在控制全身性菌血症和减少全身性炎症方面起着关键作用，从而限制了严重肺部细菌感染的全身性影响。
Kurahashi K, Sawa T, Ota M, Kajikawa O, Hong K, Martin TR, Wiener-Kronish JP. Depletion of phagocytes in the reticuloendothelial system causes increased inflammation and mortality in rabbits with Pseudomonas aeruginosa pneumonia. Am J Physiol Lung Cell Mol Physiol 296: L198-L209, 2009. First published November 21, 2008; doi:10.1152/ajplung.90472.2008.-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-alpha (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.