Blockade of LOX-1 prevents endotoxin-induced acute lung inflammation and injury in mice.
Blockade of LOX-1 prevents endotoxin-induced acute lung inflammation and injury in mice.
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DOI：
10.1159/000161070
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发表时间：
2009
影响因子：
5.3
通讯作者：
Fu J
中科院分区：
文献类型：
--
作者：
Zhang P;Liu MC;Cheng L;Liang M;Ji HL;Fu J
凝集素样氧化低密度脂蛋白（LDL）受体-1（LOX-1）是一种在内皮细胞中表达的细胞表面受体，已知其介导氧化LDL诱导的血管炎症和动脉粥样硬化形成。虽然LOX-1在血管炎症中的作用已经得到很好的证实，但其在急性肺部炎症和损伤中的作用仍不清楚。在本研究中，我们研究了LOX-1阻断抗体对小鼠内毒素脂多糖（LPS）诱导的急性肺损伤模型中肺部炎症的影响。我们证明了用LPS腹腔内攻击诱导小鼠肺中LOX-1表达的快速和稳健的增加。用抗LOX-1阻断抗体预处理小鼠显著抑制LPS诱导的肺部炎症，如肺中中性粒细胞积聚减少所示。抗LOX-1抗体还能抑制LPS诱导的小鼠肺组织炎症反应，包括NF-κ B活化、ICAM-1表达和凋亡信号。总的来说，这些结果表明LOX-1可以作为一个有价值的治疗靶点，在预防急性肺炎症和脓毒症损伤。
Lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1), a cell surface receptor expressed in endothelial cells, is known to mediate oxidized LDL-induced vascular inflammation and atherogenesis. Although the role of LOX-1 in vascular inflammation has been well established, its involvement in acute lung inflammation and injury remains unclear. In the present study, we examined the effects of a LOX-1-blocking antibody on lung inflammation in a mouse endotoxin lipopolysaccharide (LPS)-induced acute lung injury model. We demonstrated that intraperitoneal challenge with LPS induced a rapid and robust increase in LOX-1 expression in mouse lung. Pre-treatment of mice with anti-LOX-1-blocking antibody significantly inhibited LPS-induced lung inflammation as indicated by decreased neutrophil accumulation in the lung. Furthermore, anti-LOX-1 was capable of inhibiting LPS-induced inflammatory responses, including NF-κ B activation, ICAM-1 expression and apoptotic signaling, in mouse lung. Collectively, these results indicate that LOX-1 may serve as a valuable therapeutic target in the prevention of acute lung inflammation and injury in sepsis.