Receptor for advanced glycation end-products is a marker of type I cell injury in acute lung injury

Receptor for advanced glycation end-products is a marker of type I cell injury in acute lung injury
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DOI:
10.1164/rccm.200509-1477oc
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发表时间:
2006-05-01
影响因子:
24.7
通讯作者:
Matthay, MA
Matthay, MA
中科院分区:
医学1区
文献类型:
--
作者:
Uchida, T;Shirasawa, M;Matthay, MA

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基本原理:晚期糖基化终产物受体(Receptor for Advanced Glycation End-products,RECEPTOR)是肺泡Ⅰ型细胞相关蛋白之一,目的:探讨晚期糖基化终产物受体是肺泡Ⅰ型上皮细胞损伤的标志物。在大鼠支气管肺泡灌洗液(BAL)和血清中以及急性肺损伤(ALI; n = 22)和流体静力性肺水肿(n = 11)患者的肺水肿液和血浆中测定β-内酰胺酶水平。BALF中的升高水平与实验诱导的肺损伤的严重程度密切相关。在人体研究中,肺水肿液中的TNF水平显著高于血浆水平(p < 0.0001)。RAGE水平的水肿液/血浆比例中位数为105(四分位数范围,55-243)。急性肺损伤患者肺水肿液中的TNF-α水平明显高于流体静力性肺水肿患者急性肺损伤患者血浆TNF-α水平显著高于健康对照组(P < 0.05(p < 0.001)或流体静力性肺水肿患者结论:ALI大鼠和ALI患者肺泡Ⅰ型上皮细胞损伤的标志物是肺泡Ⅰ型上皮细胞损伤的标志。
Rationale: Receptor for advanced glycation end-products (RAGE) is one of the alveolar type I cell-associated proteins in the lung.Objectives: To test the hypothesis that RAGE is a marker of alveolar epithelial type I cell injury.Methods: Rats were instilled intratracheally with 10 mg/kg lipopolysaccharide or hydrochloric acid. RAGE levels were measured in the bronchoalveolar lavage (BAL) and serum in the rats and in the pulmonary edema fluid and plasma from patients with acute lung injury (ALI; n = 22) and hydrostatic pulmonary edema (n = 11).Main Results: In the rat lung injury studies, RAGE was released into the BAL and serum as a single soluble isoform sized similar to 48 kD. The elevated levels of RAGE in the BAL correlated well with the severity of experimentally induced lung injury. In the human studies, the RAGE level in the pulmonary edema fluid was significantly higher than the plasma level (p < 0.0001). The median edema fluid/plasma ratio of RAGE levels was 105 (interquartile range, 55-243). The RAGE levels in the pulmonary edema fluid from patients with ALI were higher than the levels from patients with hydrostatic pulmonary edema (p < 0.05), and the plasma RAGE level in patients with ALI were significantly higher than the healthy volunteers (p < 0.001) or patients with hydrostatic pulmonary edema (p < 0.05).Conclusion: RAGE is a marker of type I alveolar epithelial cell injury based on experimental studies in rats and in patients with ALI.