Neutralization of Osteopontin Ameliorates Acute Lung Injury Induced by Intestinal Ischemia-Reperfusion.
Neutralization of Osteopontin Ameliorates Acute Lung Injury Induced by Intestinal Ischemia-Reperfusion.
复制标题
DOI：
10.1097/shk.0000000000000611
复制
发表时间：
2016-10
期刊：
影响因子：
--
通讯作者：
Wang P
中科院分区：
文献类型：
--
作者：
Hirano Y;Aziz M;Yang WL;Ochani M;Wang P
肠道缺血再灌注（I/R）与急性呼吸窘迫综合征（ARDS）有关。骨桥蛋白（OPN）是一种由免疫反应细胞分泌的糖蛋白，在多种炎症性疾病中起着有害的作用。考虑到OPN是一种促炎分子，我们假设用其中和抗体（抗OPN Ab）治疗可保护小鼠免受肠I/R诱导的急性肺损伤（ALI）。通过用血管夹阻断小鼠的上级肠系膜动脉（SMA）来诱导肠I/R。闭塞45分钟后，取出夹子，立即静脉内给予抗OPN Ab（25 µg/小鼠）或正常IgG同种型对照（25 µg/小鼠）。在再灌注后4小时收集血液、小肠和肺组织用于各种分析。在肠I/R后，相对于假手术动物，小肠、肺和血液中OPN的mRNA和蛋白水平显著诱导。与IgG对照组相比，抗OPN Ab治疗显著降低了促炎细胞因子和趋化因子（IL-6和MIP-2）以及器官损伤标志物（AST、ALT和LDH）的血浆水平。抗OPN Ab处理的肠I/R诱导的小鼠中的肠和肺组织的组织学结构显示出相对于IgG对照小鼠的显著改善。与IgG对照小鼠相比，通过IL-6、IL-1β和MIP-2水平测量的肺部炎症在抗OPN Ab处理的小鼠中也显著下调。此外，与IgG对照动物相比，抗OPN Ab处理的小鼠中的肺MPO和中性粒细胞浸润显示出显著减少。总之，我们已经证明了抗OPN Ab治疗在预防ALI方面的有益结果，这暗示了肠道I/R的新治疗潜力。
Intestinal ischemia-reperfusion (I/R) is associated with acute respiratory distress syndrome (ARDS). Osteopontin (OPN), a glycoprotein secreted from immune-reactive cells, plays a deleterious role in various inflammatory diseases. Considering OPN as a pro-inflammatory molecule, we hypothesize that the treatment with its neutralizing antibody (anti-OPN Ab) protects mice against intestinal I/R-induced acute lung injury (ALI). Intestinal I/R was induced in mice by superior mesenteric artery (SMA) occlusion with a vascular clip. After 45 minutes of occlusion, the clip was removed and anti-OPN Ab (25 µg/mouse) or normal IgG isotype control (25 µg/mouse) was immediately administrated intravenously. Blood, small intestine, and lung tissues were collected at 4 hours after reperfusion for various analyses. After intestinal I/R, mRNA and protein levels of OPN were significantly induced in the small intestine, lungs, and blood relative to sham-operated animals. Compared with the IgG control group, treatment of anti-OPN Ab significantly reduced plasma levels of pro-inflammatory cytokine and chemokine (IL-6 and MIP-2) and organ injury markers (AST, ALT, and LDH). The histological architecture of the gut and lung tissues in anti-OPN Ab-treated intestinal I/R-induced mice showed significant improvement versus the IgG control mice. The lung inflammation measured by the levels of IL-6, IL-1β, and MIP-2 was also significantly downregulated in the anti-OPN Ab-treated mice as compared with the IgG control mice. Besides, the lung MPO and neutrophil infiltration in anti-OPN Ab-treated mice showed significant reduction as compared with the IgG control animals. In conclusion, we have demonstrated beneficial outcomes of anti-OPN Ab treatment in protecting against ALI, implicating a novel therapeutic potential in intestinal I/R.