Receptor for advanced glycation end-products (RAGE) is an indicator of direct lung injury in models of experimental lung injury

Receptor for advanced glycation end-products (RAGE) is an indicator of direct lung injury in models of experimental lung injury
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DOI:
10.1152/ajplung.90546.2008
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发表时间:
2009-07-01
影响因子:
4.9
通讯作者:
Matthay, Michael A.
Matthay, Michael A.
中科院分区:
医学2区
文献类型:
--
作者:
Su, Xiao;Looney, Mark R.;Matthay, Michael A.

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Su X,Looney MR,Gupta N,Matthay MA。晚期糖基化终末产物受体 (RAGE) 是实验性肺损伤模型中直接肺损伤的指标。 Am J Physiol Lung Cell Mol Physiol 297:L1-L5,2009。首次发表于 2009 年 5 月 1 日; doi: 10.1152/ajplung.90546.2008.-晚期糖基化终末产物受体 (RAGE) 是肺泡 I 型细胞的标志物,在急性肺损伤 (ALI) 患者的肺水肿液中升高。我们测试了这样的假设:在以肺泡上皮细胞损伤为特征的直接 ALI 实验模型中,支气管肺泡灌洗 (BAL) 中的 RAGE 会升高。我们开发了 RAGE 的 ELISA 测量方法,并研究了 ALI(直接和间接)小鼠模型,并在指定终点收集了 BAL 以测量 RAGE。我们还测试了 BAL RAGE 水平是否与 1) 与酸和高氧诱导的 ALI 中肺损伤的严重程度相关,以及 2) 与新疗法间充质干细胞 (MSC) 在 LPS 诱导的 ALI 中的有益效果相关。在由气管内滴注酸、LPS或大肠杆菌诱导的直接肺损伤的ALI模型中,BAL RAGE分别升高58倍、22倍和13倍。相比之下,在腹腔注射硫脲或静脉注射 MHC I 单克隆抗体(产生输血相关 ALI 小鼠模型)诱导的 ALI 间接模型中,未检测到 BAL RAGE。 BAL RAGE 确实与酸和高氧诱导的 ALI 中肺损伤的严重程度相关。此外,对于 LPS 诱导的 ALI,MSC 治疗后的 BAL RAGE 显着降低。总之,BAL RAGE 是 ALI 的一个指标,它可能有助于区分 ALI 的直接模型和间接模型以及评估对特定治疗的反应。
Su X, Looney MR, Gupta N, Matthay MA. Receptor for advanced glycation end-products (RAGE) is an indicator of direct lung injury in models of experimental lung injury. Am J Physiol Lung Cell Mol Physiol 297: L1-L5, 2009. First published May 1, 2009; doi: 10.1152/ajplung.90546.2008.-Receptor for advanced glycation end-products (RAGE) is a marker of alveolar type I cells and is elevated in the pulmonary edema fluid of patients with acute lung injury (ALI). We tested the hypothesis that RAGE in the bronchoalveolar lavage (BAL) would be elevated in experimental models of direct ALI characterized by alveolar epithelial cell injury. We developed ELISA measurements for RAGE and studied ALI (direct and indirect) mouse models and collected BAL at specified endpoints to measure RAGE. We also tested whether levels of BAL RAGE correlated 1) with the severity of lung injury in acid and hyperoxia-induced ALI and 2) with the beneficial effect of a novel treatment, mesenchymal stem cells (MSC), in LPS-induced ALI. In ALI models of direct lung injury induced by intratracheal instillation of acid, LPS, or Escherichia coli, the BAL RAGE was 58-, 22-, and 13-fold elevated, respectively. In contrast, BAL RAGE was not detectable in indirect models of ALI induced by an intraperitoneal injection of thiourea or by an intravenous injection of MHC I monoclonal antibody that produces a mouse model of transfusion-related ALI. BAL RAGE did correlate with the severity of lung injury in acid and hyperoxia-induced ALI. In addition, with LPS-induced ALI, BAL RAGE was markedly reduced with MSC treatment. In summary, BAL RAGE is an indicator of ALI, and it may be useful in distinguishing direct from indirect models of ALI as well as assessing the response to specific therapies.