Adenovirus-Delivered Angiopoietin 1 Accelerates the Resolution of Inflammation of Acute Endotoxic Lung Injury in Mice
Adenovirus-Delivered Angiopoietin 1 Accelerates the Resolution of Inflammation of Acute Endotoxic Lung Injury in Mice
复制标题
腺病毒递送的血管生成素1加速小鼠急性内毒素性肺损伤炎症的消退
DOI：
10.1213/ane.0b013e318213fbd3
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发表时间：
2011-06-01
影响因子：
5.7
通讯作者：
Zhang, Shi-Hai
中科院分区：
文献类型：
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作者：
Xu, You-Nian;Zhang, Zhao;Zhang, Shi-Hai
背景：免疫系统在保护机体免受感染方面起着关键作用。及时解决对感染的炎症反应在恢复体内平衡和维持正常器官功能方面起着至关重要的作用。血管生成素1可防止内皮细胞活化，这是对病原体的炎症反应的一部分，并在急性肺损伤中具有抗炎作用。我们设计了这项研究，以探讨是否增加血清生产的血管生成素1的腺病毒递送的血管生成素1可以加速内毒素诱导的急性肺injury in mice.METHODS：脂多糖intrichelially滴注诱导急性肺损伤的动物预处理24小时与腺病毒-GFP载体或腺病毒-GFP-血管生成素1，分别。在脂多糖滴注之前，每个预处理组中另外6只小鼠被处死以用作对照。分析炎症消退指数。用荧光激活细胞分选仪测定凋亡的多形核白细胞及其被巨噬细胞吞噬的能力。结果：脂多糖可诱导白细胞浸润，48 h后浸润最多，48 h后达高峰，48 h后再行肺泡灌洗液中粒细胞巨噬细胞集落刺激因子（GM-CSF）的检测。用腺病毒-GFP-血管生成素1预处理显著增加血管生成素1表达，减少白细胞和中性粒细胞浸润，缩短炎症持续时间。腺病毒-GFP-angiopoietin 1预处理增强的幅度，而不改变的时间过程中的粒细胞-巨噬细胞集落刺激因子。结论：我们的研究结果表明，angiopoietin 1预处理促进决议炎症内毒素诱导的急性肺损伤小鼠通过加速中性粒细胞的凋亡和巨噬细胞的吞噬作用。（Anesth Analg 2011; 112：1403-10）
BACKGROUND: The immune system plays a key role in protecting the organism from infection. Timely resolution of the inflammatory response to infection plays a vital role in returning homeostasis and maintaining normal organ function. Angiopoietin1 prevents endothelial activation, part of the inflammatory response to a pathogen, and has an anti-inflammatory effect in acute lung injury. We designed this study to investigate whether increasing serum production of angiopoietin1 by IV administration of adenoviral-delivered angiopoietin1 could accelerate the resolution of inflammation in endotoxin-induced acute lung injury in mice.METHODS: Lipopolysaccharide was intratracheally instilled to induce acute lung injury in animals pretreated for 24 hours with adenoviral-GFP vector or adenoviral-GFP-angiopoietin1, respectively. An additional 6 mice in each pretreatment group were killed before lipopolysaccharide instillation to serve as controls. Indices of resolution of inflammation were analyzed. Apoptotic polymorphonuclear leukocytes and their phagocytosis by macrophages were determined by fluorescent activated cell sorter. The expression of angiopoietin1 in tissues and granulocyte macrophage colony-stimulating factor in the bronchoalveolar lavage fluid were measured.RESULTS: Lipopolysaccharide induced leukocyte infiltration into air spaces, with maximal infiltration 48 hours after lipopolysaccharide instillation. Pretreatment with adenovirus-GFP-angiopoietin1 markedly increased angiopoietin1 expression, reduced leukocyte, and neutrophil infiltration and shortened the duration of inflammation. Adenovirus-GFP-angiopoietin1 pretreatment augmented the magnitude without altering the time course of granulocyte macrophage colony-stimulating factor.CONCLUSIONS: Our results suggest that angiopoietin1 pretreatment promotes resolution of inflammation in endotoxin-induced acute lung injury in mice by accelerating the apoptosis of neutrophils and their phagocytosis by macrophages. (Anesth Analg 2011; 112: 1403-10)