Effects of Cl2MDP-encapsulating liposomes in a murine model of Pseudomonas aeruginosa-induced sepsis.
Effects of Cl2MDP-encapsulating liposomes in a murine model of Pseudomonas aeruginosa-induced sepsis.
复制标题
Cl2MDP 封装脂质体对铜绿假单胞菌诱导脓毒症小鼠模型的影响。
DOI:
10.1081/lpr-120014760
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发表时间:
2002
影响因子:
4.4
通讯作者:
Sawa,Teiji
中科院分区:
文献类型:
--
作者:
Fujimoto,Junichi;Wiener-Kronish,JeanineP;Hashimoto,Satoru;Sawa,Teiji
Pseudomonas aeruginosais a pathogen that frequently causes acute lung injury, bacteremia and sepsis in critically ill patients. As tissue macrophages are a major producer of inflammatory mediators that contribute to septic physiology, and are essential for eliminating bacteria from the circulation, we investigated the role of tissue macrophages in the generation of both inflammatory and anti-inflammatory cytokines in septic shock by using our mouse model ofP. aeruginosapneumonia. To see the effects of tissue macrophage depletion, we intravenously injected dichloromethylene-diphosphonate (Cl2MDP)-encapsulating liposomes in mice. Two days after the liposome injection, we instilled cytotoxicP. aeruginosa(PA103) into the lung that disseminates and causes septic shock. After the infection, we collected blood and bronchoalveolar lavage fluids. The samples were then analyzed for TNF-α, MIP-2, and IL-10 concentration. We compared these results to control mice that received either liposomes without Cl2MDP or phosphate buffered saline alone. Plasma TNF-α, MIP-2, and IL-10 levels were significantly decreased in the tissue macrophage-depleted mice compared to the control groups of mice. Although depletion of tissue macrophages by Cl2MDP-liposome administration did not affect the severity of bacteremia or the survival of infected mice, these results imply that tissue macrophages have a major role in the production of both proinflammatory and anti-inflammatory cytokines in the circulation and in the causing septic physiology associated withP. aeruginosapneumonia.