Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA.
J Innate Immun. 2009;1(4):358-65. doi: 10.1159/000161070. Epub 2008 Oct 1.
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-kappaB 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.
凝集素样氧化型低密度脂蛋白（LDL）受体-1（LOX-1）是一种表达在血管内皮细胞表面的细胞表面受体，已知其介导氧化型 LDL 诱导的血管炎症和动脉粥样硬化形成。尽管 LOX-1 在血管炎症中的作用已得到充分证实，但它在急性肺炎症和损伤中的作用尚不清楚。在本研究中，我们研究了 LOX-1 阻断抗体对 LPS 诱导的急性肺损伤小鼠模型中肺炎症的影响。我们证明了 LPS 腹腔内挑战可迅速而强烈地诱导小鼠肺中 LOX-1 的表达增加。用抗 LOX-1 阻断抗体预处理小鼠可显著抑制 LPS 诱导的肺炎症，表现为肺内中性粒细胞积聚减少。此外，抗 LOX-1 能够抑制 LPS 诱导的炎症反应，包括 NF-κB 激活、ICAM-1 表达和凋亡信号通路，在小鼠肺中。总之，这些结果表明 LOX-1 可能是预防脓毒症急性肺炎症和损伤的有价值的治疗靶点。
