Depletion of alveolar macrophages by clodronate-liposomes aggravates ischemia-reperfusion injury of the lung
Depletion of alveolar macrophages by clodronate-liposomes aggravates ischemia-reperfusion injury of the lung
复制标题
DOI：
10.1016/j.healun.2003.10.007
复制
发表时间：
2005-01-01
影响因子：
8.9
通讯作者：
Schäfers, HJ
中科院分区：
文献类型：
--
作者：
Nakamura, T;Abu-Dahab, R;Schäfers, HJ
背景：巨噬细胞在多种器官的缺血再灌注损伤中起重要作用。脂质体包封的二氯亚甲基二膦酸盐（氯膦酸盐-脂质体）在体内消耗局部巨噬细胞。然而，这种方法对肺泡巨噬细胞在肺缺血-再灌注injuries.Methods：氯膦酸盐脂质体在汉克斯平衡盐溶液（HBSS）或HBSS单独给气管内注射给麻醉的雄性刘易斯大鼠或对照组（n = 6/每组）。3天后，我们在离体血液灌注大鼠肺模型中对肺进行缺血（37 ℃，60分钟）和再灌注（60分钟）。再灌注期间的分析包括气体交换、血流动力学和气道力学。结果：氯膦酸二钠组在再灌注10 min内有4次实验因肺损伤严重而终止，而对照组在再灌注60 min内所有肺均可观察到（p < 0.05）。氯膦酸二钠显著降低气道动态顺应性（p < 0.05），增加气道阻力。除了肺血管阻力增加的趋势外，这与多形核中性粒细胞的募集有关支气管肺泡灌洗液中MIP-2浓度增加（p < 0.05）（P < 0.05）。脂质体包封的氯膦酸盐的肠内给药没有益处，但减轻了肺的热缺血再灌注损伤，增加MIP-2相关的肺泡中性粒细胞募集和气道机械功能障碍。国际心肺移植学会版权所有（C）2005。
Background: Macrophages play an important role in ischemia-reperfusion injury of various organs. Liposome-encapsulated dichloromethylene diphosphonate (clodronate-liposome) depletes local macrophages in vivo. However, the effect of this approach on alveolar macrophages in pulmonary ischemia-reperfusion injury has not yet been evaluated.Methods: Clodronate-liposomes in Hanks' balanced salt solution (HBSS) or HBSS alone were given intratracheally to anesthetized male Lewis rats in the clodronate or the control group (n = 6/each group). After 3 days, we subjected the lungs to ischemia (37degreesC, 60 minutes) and reperfusion (60 minutes) in an isolated blood-perfused rat lung model. Analysis during reperfusion included gas exchange, hemodynamics, and airway mechanics. At the end of reperfusion, we determined leukocyte recruitment and macrophage inflammatory protein-2 (MIP-2) in bronchoalveolar lavage fluid.Results: In the clodronate group, 4 experiments had to be terminated within 10 minutes of reperfusion because of severe lung injury, whereas all lungs of the controls could be studied during the 60-minute reperfusion period (p < 0.05). Clodronate significantly decreased dynamic airway compliance (p < 0.05) and increased airway resistance. Besides a tendency toward greater pulmonary vascular resistance, this was associated with recruitment of polymorphonuclear neutrophils (p < 0.05) and increased MIP-2 concentrations in the bronchoalveolar lavage fluid (P < 0.05).Conclusions: Intratracheal administration of liposome-encapsulated clodronate does not benefit, but aggravates, warm ischemia-reperfusion injury of the lung, increasing MIP-2-associated alveolar neutrophil recruitment and airway mechanical dysfunction. Copyright (C) 2005 by the International Society for Heart and Lung Transplantation.