Alveolar macrophage activation is a key initiation signal for acute lung ischemia-reperfusion injury
Alveolar macrophage activation is a key initiation signal for acute lung ischemia-reperfusion injury
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DOI：
10.1152/ajplung.00086.2006
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发表时间：
2006-11-01
影响因子：
4.9
通讯作者：
Laubach, Victor E.
中科院分区：
文献类型：
--
作者：
Zhao, Minqing;Fernandez, Lucas G.;Laubach, Victor E.
肺泡巨噬细胞激活是急性肺缺血再灌注损伤的关键起始信号。 Am J Physiol Lung Cell Mol Physiol 291：L1018-L1026，2006。首次发表于 2006 年 7 月 21 日； doi:10.1152/ajplung.00086.2006.-肺缺血再灌注（I/R）损伤是一个双相炎症过程。先前的研究表明，后期是中性粒细胞依赖性的，肺泡巨噬细胞（AM）可能导致肺 I/R 损伤的急性期。然而，其机制尚不清楚。 AM 在许多炎症反应（包括移植）中被激活并产生各种细胞因子和趋化因子。我们假设 AMs 通过产生关键细胞因子和趋化因子来响应 I/R，并且 AMs 的消耗将减少 I/R 后细胞因子/趋化因子的表达和肺损伤。为了测试这一点，我们使用缓冲液灌注的离体小鼠肺模型，研究了脂质体氯膦酸盐的 AM 消耗对 I/R 诱导的肺功能障碍/损伤以及细胞因子/趋化因子表达的影响。与假肺相比，I/R导致肺动脉压、湿干重比、血管通透性、肿瘤坏死因子（TNF）-α、单核细胞趋化蛋白（MCP）-1和巨噬细胞炎症蛋白（MIP）-2表达显着增加，以及肺顺应性降低。 AM 耗尽后，I/R 组和假手术组之间每个参数的变化均显着减弱。因此，AM 消耗可以保护肺部免受缺血再灌注引起的功能障碍和损伤，并显着减少细胞因子/趋化因子的产生。 TNF-α和MCP-1的蛋白表达与缺血再灌注引起的肺损伤呈正相关，AMs是TNF-α、MCP-1和MIP-2的主要产生者/引发者。我们得出的结论是，AMs 在引发急性肺 I/R 损伤中发挥着重要作用。
Alveolar macrophage activation is a key initiation signal for acute lung ischemia-reperfusion injury. Am J Physiol Lung Cell Mol Physiol 291: L1018-L1026, 2006. First published July 21, 2006; doi:10.1152/ajplung.00086.2006.-Lung ischemia-reperfusion (I/R) injury is a biphasic inflammatory process. Previous studies indicate that the later phase is neutrophil-dependent and that alveolar macrophages (AMs) likely contribute to the acute phase of lung I/R injury. However, the mechanism is unclear. AMs become activated and produce various cytokines and chemokines in many inflammatory responses, including transplantation. We hypothesize that AMs respond to I/R by producing key cytokines and chemokines and that depletion of AMs would reduce cytokine/ chemokine expression and lung injury after I/R. To test this, using a buffer-perfused, isolated mouse lung model, we studied the impact of AM depletion by liposome-clodronate on I/R-induced lung dysfunction/ injury and expression of cytokines/chemokines. I/R caused a significant increase in pulmonary artery pressure, wet-to-dry weight ratio, vascular permeability, tumor necrosis factor (TNF)-alpha, monocyte chemoattractant protein (MCP)-1, and macrophage inflammatory protein (MIP)-2 expression, as well as decreased pulmonary compliance, when compared with sham lungs. After AM depletion, the changes in each of these parameters between I/R and sham groups were significantly attenuated. Thus AM depletion protects the lungs from I/R-induced dysfunction and injury and significantly reduces cytokine/ chemokine production. Protein expression of TNF-alpha and MCP-1 are positively correlated to I/R-induced lung injury, and AMs are a major producer/initiator of TNF-alpha, MCP-1, and MIP-2. We conclude that AMs are an essential player in the initiation of acute lung I/R injury.